Catheter Apparatuses, Systems, and Methods for Renal Neuromodulation

ABSTRACT

Catheter apparatuses, systems, and methods for achieving renal neuromodulation by intravascular access are disclosed herein. One aspect of the present application, for example, is directed to apparatuses, systems, and methods that incorporate a catheter treatment device comprising an elongated shaft. The elongated shaft is sized and configured to deliver an energy delivery element to a renal artery via an intravascular path. Thermal or electrical renal neuromodulation may be achieved via direct and/or via indirect application of thermal and/or electrical energy to heat or cool, or otherwise electrically modulate, neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers.

REFERENCE TO RELATED APPLICATION(S)

The present application is a continuation of U.S. patent applicationSer. No. 14/316,122, filed on Jun. 26, 2014, which is a continuation ofU.S. patent application Ser. No. 12/790,639, filed May 28, 2010, nowU.S. Pat. No. 8,870,863, which claims the benefit of U.S. ProvisionalPatent Application No. 61/328,105, filed Apr. 26, 2010. The disclosuresof all of these applications are incorporated herein by reference intheir entireties.

TECHNICAL FIELD

The technologies disclosed in the present application generally relateto catheter apparatuses, systems and methods for intravascularneuromodulation. More particularly, the technologies disclosed hereinrelate to catheter apparatuses, systems, and methods for achievingintravascular renal neuromodulation via application of thermal and/orelectrical energy.

BACKGROUND

Hypertension, heart failure, chronic kidney disease, insulin resistance,diabetes and metabolic syndrome represent a significant and growingglobal health issue. Current therapies for these conditions includenon-pharmacological, pharmacological and device-based approaches.Despite this variety of treatment options, the rates of control of bloodpressure and the therapeutic efforts to prevent progression of thesedisease states and their sequelae remain unsatisfactory. Although thereasons for this situation are manifold and include issues ofnon-compliance with prescribed therapy, heterogeneity in responses bothin terms of efficacy and adverse event profile, and others, it isevident that alternative options are required to supplement the currenttherapeutic treatment regimes for these conditions.

Reduction of sympathetic renal nerve activity (e.g., via denervation),can reverse these processes. Ardian, Inc., of Palo Alto, Calif., hasdiscovered that an energy field, including and comprising an electricfield, can initiate renal neuromodulation via denervation caused byirreversible electroporation, electrofusion, apoptosis, necrosis,ablation, thermal alteration, alteration of gene expression or anothersuitable modality.

Catheter-based intervention is widely used for medical treatments whereaccess to a location in the body is obtained, for example, through avessel of the cardiovascular system. Ardian, Inc. has shown that anenergy field can be applied to the sympathetic renal nerves from withina renal artery. The renal artery has features unique from other vesselsor parts of the body and thus applying an energy field to thesympathetic renal nerves from within the renal artery is not trivial.Accordingly, a need exists for a catheter capable of effectivelydelivering energy to the renal sympathetic nerves from within a renalartery, where the catheter is better configured to i) navigate through arenal artery with reduced risk of applying traumatic force to the arterywall; ii) precisely place an energy delivery element at a desiredlocation on the vessel wall; and iii) maintain stable contact betweenthe energy delivery element and the location on the vessel wall duringblood flow pulsatility and respiratory motion of the renal artery.

SUMMARY

The following summary is provided for the benefit of the reader only,and is not intended to limit the disclosure in any way. The presentapplication provides catheter apparatuses, systems and methods forachieving electrically- and/or thermally-induced renal neuromodulationby intravascular access.

One aspect of the present application provides apparatuses, systems, andmethods that incorporate a catheter treatment device comprising anelongated shaft. The elongated shaft is sized and configured to deliverat least one energy delivery element to a renal artery via anintravascular path that includes a femoral artery, an iliac artery andthe aorta. Different sections of the elongated shaft serve differentmechanical functions when in use. The sections are differentiated interms of their size, configuration, and mechanical properties for (i)percutaneous introduction into a femoral or brachial artery through asmall-diameter access site; (ii) atraumatic passage through the tortuousintravascular path through an iliac artery, into the aorta, and into arespective left/right renal artery, including (iii) accommodatingsignificant flexure at the junction of the left/right renal arteries andaorta to gain entry into the respective left or right renal artery; (iv)accommodating controlled translation, deflection, and/or rotation withinthe respective renal artery to attain proximity to and a desiredalignment with an interior wall of the respective renal artery; (v)allowing the placement of at least one energy delivery element intocontact with tissue on the interior wall in an orientation thatoptimizes the active surface area of the energy delivery element; and(vi) allowing substantially stable contact force between the at leastone energy delivery element and the interior wall during motion of therenal artery with respect to the aorta due to respiration and/or bloodflow pulsatility.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a conceptual illustration of the sympathetic nervous system(SNS) and how the brain communicates with the body via the SNS.

FIG. 2 is an enlarged anatomic view of nerves innervating a left kidneyto form the renal plexus surrounding the left renal artery.

FIGS. 3A and 3B provide anatomic and conceptual views of a human body,respectively, depicting neural efferent and afferent communicationbetween the brain and kidneys

FIGS. 4A and 4B are, respectively, anatomic views of the arterial andvenous vasculatures of a human.

FIG. 5 is a perspective view of a system for achieving intravascular,thermally-induced renal neuromodulation, comprising a treatment deviceand a generator.

FIGS. 6A to 6C are anatomic views of the intravascular delivery,deflection and placement of various embodiments of the treatment deviceshown in FIG. 5 through the femoral artery and into a renal artery.

FIGS. 7A to 7D are a series of views of the elongated shaft of thetreatment device shown in FIG. 5, showing the different mechanical andfunctional regions that the elongated shaft incorporates.

FIG. 8A shows an anatomic view of the advancement of a treatment devicewithout the features of the present invention within a renal artery.

FIGS. 8B to 8D show an anatomic view of the placement of the treatmentdevice shown in FIG. 5 within the dimensions of the renal artery.

FIGS. 9A to 9D show force vectors of trajectories of a straight catheter(not of the present invention) advancing into a soft wall and theresultant forces.

FIGS. 10A to 10E show examples of configurations of force redirectingelements.

FIGS. 11A to 11B show the placement of an energy delivery element, whichis carried at the distal end of the elongated shaft of the treatmentdevice shown in FIG. 5, into contact with tissue along a renal artery.

FIGS. 12A and 12B show placement of the energy delivery element shown inFIGS. 11A to 11B into contact with tissue along a renal artery anddelivery of thermal treatment to the renal plexus.

FIGS. 13A and 13B show a representative embodiment of the forcetransmitting section of the elongated shaft of the treatment deviceshown in FIG. 5.

FIGS. 14A to 14C show a representative embodiment of the first flexurezone of the elongated shaft of the treatment device shown in FIG. 5.

FIGS. 15A to 15D show a representative embodiment of the deflectablesection of the elongated shaft of the treatment device shown in FIG. 5.

FIGS. 16A to 16C show a representative embodiment of the force dampeningsection of the elongated shaft of the treatment device shown in FIG. 5.

FIGS. 16D to 16F show multiple planar views of the bending capability ofthe force dampening section corresponding to the elongated shaft of thetreatment device shown in FIG. 5.

FIGS. 16G and 16H show alternative embodiments of the force dampeningsection corresponding to the elongated shaft of the treatment deviceshown in FIG. 5.

FIGS. 17A and 17B show a representative embodiment of a rotationalcontrol mechanism coupled to the handle assembly of the treatment deviceshown in FIG. 5.

FIGS. 18A to 18G show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 19A to 19D show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 20A to 20D show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 21A to 21C show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 22A to 22G show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 23A to 23D show additional alternative representative embodimentsof an elongated shaft for a treatment device like that shown in FIG. 5,showing examples of the different structural, mechanical and functionalregions that the elongated shaft can incorporate.

FIGS. 24A to 24H show the intravascular delivery, placement, deflection,rotation, retraction, repositioning and use of a treatment device, likethat shown in FIG. 5, to achieve thermally-induced renal neuromodulationfrom within a renal artery.

FIGS. 24I to 24K show the circumferential treatment effect resultingfrom intravascular use of a treatment device, like that shown in FIG. 5.

FIG. 24L shows an alternative intravascular treatment approach using atreatment device, like that shown in FIG. 5.

FIG. 25 shows an energy delivery algorithm corresponding to the energygenerator of a system, like that shown in FIG. 5.

FIG. 26 shows several components of a system and treatment device, likethat shown in FIG. 5, packaged within a single kit.

FIGS. 27A to 27C show fluoroscopic images of a treatment device, likethat shown in FIG. 5 but without a force redirecting element, inmultiple treatment positions within a renal artery of an animal.

FIGS. 27D and 27E show fluoroscopic images of a treatment device, likethat shown in FIG. 5 but without a force redirecting element, inmultiple treatment positions within a renal artery during a human study.

DETAILED DESCRIPTION

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the disclosed technologies, the physicalembodiments herein disclosed merely exemplify the various aspects of theinvention, which may be embodied in other specific structures. While thepreferred embodiment has been described, the details may be changedwithout departing from the invention, which is defined by the claims.

I. PERTINENT ANATOMY AND PHYSIOLOGY A. The Sympathetic Nervous System

The Sympathetic Nervous System (SNS) is a branch of the autonomicnervous system along with the enteric nervous system and parasympatheticnervous system. It is always active at a basal level (called sympathetictone) and becomes more active during times of stress. Like other partsof the nervous system, the sympathetic nervous system operates through aseries of interconnected neurons. Sympathetic neurons are frequentlyconsidered part of the peripheral nervous system (PNS), although manylie within the central nervous system (CNS). Sympathetic neurons of thespinal cord (which is part of the CNS) communicate with peripheralsympathetic neurons via a series of sympathetic ganglia. Within theganglia, spinal cord sympathetic neurons join peripheral sympatheticneurons through synapses. Spinal cord sympathetic neurons are thereforecalled presynaptic (or preganglionic) neurons, while peripheralsympathetic neurons are called postsynaptic (or postganglionic) neurons.

At synapses within the sympathetic ganglia, preganglionic sympatheticneurons release acetylcholine, a chemical messenger that binds andactivates nicotinic acetylcholine receptors on postganglionic neurons.In response to this stimulus, postganglionic neurons principally releasenoradrenaline (norepinephrine). Prolonged activation can elicit therelease of adrenaline from the adrenal medulla.

Once released, norepinephrine and epinephrine bind adrenergic receptorson peripheral tissues. Binding to adrenergic receptors causes a neuronaland hormonal response. The physiologic manifestations include pupildilation, increased heart rate, occasional vomiting, and increased bloodpressure. Increased sweating is also seen due to binding of cholinergicreceptors of the sweat glands.

The sympathetic nervous system is responsible for up- anddown-regulating many homeostatic mechanisms in living organisms. Fibersfrom the SNS innervate tissues in almost every organ system, providingat least some regulatory function to things as diverse as pupildiameter, gut motility, and urinary output. This response is also knownas sympatho-adrenal response of the body, as the preganglionicsympathetic fibers that end in the adrenal medulla (but also all othersympathetic fibers) secrete acetylcholine, which activates the secretionof adrenaline (epinephrine) and to a lesser extent noradrenaline(norepinephrine). Therefore, this response that acts primarily on thecardiovascular system is mediated directly via impulses transmittedthrough the sympathetic nervous system and indirectly via catecholaminessecreted from the adrenal medulla.

Science typically looks at the SNS as an automatic regulation system,that is, one that operates without the intervention of consciousthought. Some evolutionary theorists suggest that the sympatheticnervous system operated in early organisms to maintain survival as thesympathetic nervous system is responsible for priming the body foraction. One example of this priming is in the moments before waking, inwhich sympathetic outflow spontaneously increases in preparation foraction.

1. The Sympathetic Chain

As shown in FIG. 1, the SNS provides a network of nerves that allows thebrain to communicate with the body. Sympathetic nerves originate insidethe vertebral column, toward the middle of the spinal cord in theintermediolateral cell column (or lateral horn), beginning at the firstthoracic segment of the spinal cord and are thought to extend to thesecond or third lumbar segments. Because its cells begin in the thoracicand lumbar regions of the spinal cord, the SNS is said to have athoracolumbar outflow. Axons of these nerves leave the spinal cordthrough the anterior rootlet/root. They pass near the spinal (sensory)ganglion, where they enter the anterior rami of the spinal nerves.However, unlike somatic innervation, they quickly separate out throughwhite rami connectors which connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near theaortic bifurcation) ganglia extending alongside the spinal column.

In order to reach the target organs and glands, the axons must travellong distances in the body, and, to accomplish this, many axons relaytheir message to a second cell through synaptic transmission. The endsof the axons link across a space, the synapse, to the dendrites of thesecond cell. The first cell (the presynaptic cell) sends aneurotransmitter across the synaptic cleft where it activates the secondcell (the postsynaptic cell). The message is then carried to the finaldestination.

In the SNS and other components of the peripheral nervous system, thesesynapses are made at sites called ganglia. The cell that sends its fiberis called a preganglionic cell, while the cell whose fiber leaves theganglion is called a postganglionic cell. As mentioned previously, thepreganglionic cells of the SNS are located between the first thoracic(T1) segment and third lumbar (L3) segments of the spinal cord.Postganglionic cells have their cell bodies in the ganglia and sendtheir axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also thecervical ganglia (superior, middle and inferior), which sendssympathetic nerve fibers to the head and thorax organs, and the celiacand mesenteric ganglia (which send sympathetic fibers to the gut).

2. Innervation of the Kidneys

As FIG. 2 shows, the kidney is innervated by the renal plexus (RP),which is intimately associated with the renal artery. The renal plexusis an autonomic plexus that surrounds the renal artery and is embeddedwithin the adventitia of the renal artery. The renal plexus extendsalong the renal artery until it arrives at the substance of the kidney.Fibers contributing to the renal plexus arise from the celiac ganglion,the superior mesenteric ganglion, the aorticorenal ganglion and theaortic plexus. The renal plexus (RP), also referred to as the renalnerve, is predominantly comprised of sympathetic components. There is no(or at least very minimal) parasympathetic innervation of the kidney.

Preganglionic neuronal cell bodies are located in the intermediolateralcell column of the spinal cord. Preganglionic axons pass through theparavertebral ganglia (they do not synapse) to become the lessersplanchnic nerve, the least splanchnic nerve, first lumbar splanchnicnerve, second lumbar splanchnic nerve, and travel to the celiacganglion, the superior mesenteric ganglion, and the aorticorenalganglion. Postganglionic neuronal cell bodies exit the celiac ganglion,the superior mesenteric ganglion, and the aorticorenal ganglion to therenal plexus (RP) and are distributed to the renal vasculature.

3. Renal Sympathetic Neural Activity

Messages travel through the SNS in a bidirectional flow. Efferentmessages can trigger changes in different parts of the bodysimultaneously. For example, the sympathetic nervous system canaccelerate heart rate; widen bronchial passages; decrease motility(movement) of the large intestine; constrict blood vessels; increaseperistalsis in the esophagus; cause pupil dilation, piloerection (goosebumps) and perspiration (sweating); and raise blood pressure. Afferentmessages carry signals from various organs and sensory receptors in thebody to other organs and, particularly, the brain.

Hypertension, heart failure and chronic kidney disease are a few of manydisease states that result from chronic activation of the SNS,especially the renal sympathetic nervous system. Chronic activation ofthe SNS is a maladaptive response that drives the progression of thesedisease states. Pharmaceutical management of therenin-angiotensin-aldosterone system (RAAS) has been a longstanding, butsomewhat ineffective, approach for reducing over-activity of the SNS.

As mentioned above, the renal sympathetic nervous system has beenidentified as a major contributor to the complex pathophysiology ofhypertension, states of volume overload (such as heart failure), andprogressive renal disease, both experimentally and in humans. Studiesemploying radiotracer dilution methodology to measure overflow ofnorepinephrine from the kidneys to plasma revealed increased renalnorepinephrine (NE) spillover rates in patients with essentialhypertension, particularly so in young hypertensive subjects, which inconcert with increased NE spillover from the heart, is consistent withthe hemodynamic profile typically seen in early hypertension andcharacterized by an increased heart rate, cardiac output andrenovascular resistance. It is now known that essential hypertension iscommonly neurogenic, often accompanied by pronounced sympathetic nervoussystem overactivity.

Activation of cardiorenal sympathetic nerve activity is even morepronounced in heart failure, as demonstrated by an exaggerated increaseof NE overflow from the heart and the kidneys to plasma in this patientgroup. In line with this notion is the recent demonstration of a strongnegative predictive value of renal sympathetic activation on all-causemortality and heart transplantation in patients with congestive heartfailure, which is independent of overall sympathetic activity,glomerular filtration rate and left ventricular ejection fraction. Thesefindings support the notion that treatment regimens that are designed toreduce renal sympathetic stimulation have the potential to improvesurvival in patients with heart failure.

Both chronic and end stage renal disease are characterized by heightenedsympathetic nervous activation. In patients with end stage renaldisease, plasma levels of norepinephrine above the median have beendemonstrated to be predictive for both all cause death and death fromcardiovascular disease. This is also true for patients suffering fromdiabetic or contrast nephropathy. There is compelling evidence thatsuggests that sensory afferent signals originating from the diseasedkidneys are major contributors to the initiation and sustainment ofelevated central sympathetic outflow in this patient group, whichfacilitates the occurrence of the well known adverse consequences ofchronic sympathetic overactivity such as hypertension, left ventricularhypertrophy, ventricular arrhythmias, sudden cardiac death, insulinresistance, diabetes and metabolic syndrome.

(i) Renal Sympathetic Efferent Activity

Sympathetic nerves to the kidneys terminate in the blood vessels, thejuxtaglomerular apparatus and the renal tubules. Stimulation of therenal sympathetic nerves causes increased renin release, increasedsodium (Na+) reabsorption and a reduction of renal blood flow. Thesecomponents of the neural regulation of renal function are considerablystimulated in disease states characterized by heightened sympathetictone and clearly contribute to the rise in blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome, which is renal dysfunction as a progressive complication ofchronic heart failure, with a clinical course that typically fluctuateswith the patient's clinical status and treatment. Pharmacologicstrategies to thwart the consequences of renal efferent sympatheticstimulation include centrally acting sympatholytic drugs, beta blockers(intended to reduce renin release), angiotensin converting enzymeinhibitors and receptor blockers (intended to block the action ofangiotensin II and aldosterone activation consequent to renin release)and diuretics (intended to counter the renal sympathetic mediated sodiumand water retention). However, the current pharmacologic strategies havesignificant limitations including limited efficacy, compliance issues,side effects and others.

(ii) Renal Sensory Afferent Nerve Activity

The kidneys communicate with integral structures in the central nervoussystem via renal sensory afferent nerves. Several forms of “renalinjury” can induce activation of sensory afferent signals. For example,renal ischemia, reduction in stroke volume or renal blood flow, or anabundance of adenosine enzyme may trigger activation of afferent neuralcommunication. As shown in FIGS. 3A and 3B, this afferent communicationmight be from the kidney to the brain or might be from one kidney to theother kidney (via the central nervous system). These afferent signalsare centrally integrated and can result in increased sympatheticoutflow. This sympathetic drive is directed towards the kidneys, therebyactivating the RAAS and inducing increased renin secretion, sodiumretention, volume retention and vasoconstriction. Central sympatheticoveractivity also impacts other organs and bodily structures innervatedby sympathetic nerves such as the heart and the peripheral vasculature,resulting in the described adverse effects of sympathetic activation,several aspects of which also contribute to the rise in blood pressure.

The physiology therefore suggests that (i) denervation of tissue withefferent sympathetic nerves will reduce inappropriate renin release,salt retention, and reduction of renal blood flow, and that (ii)denervation of tissue with afferent sensory nerves will reduce thesystemic contribution to hypertension, and other disease statesassociated with increased central sympathetic tone, through its directeffect on the posterior hypothalamus as well as the contralateralkidney. In addition to the central hypotensive effects of afferent renaldenervation, a desirable reduction of central sympathetic outflow tovarious other sympathetically innervated organs such as the heart andthe vasculature is anticipated.

B. Additional Clinical Benefits of Renal Denervation

As provided above, renal denervation is likely to be valuable in thetreatment of several clinical conditions characterized by increasedoverall and particularly renal sympathetic activity such ashypertension, metabolic syndrome, insulin resistance, diabetes, leftventricular hypertrophy, chronic and end stage renal disease,inappropriate fluid retention in heart failure, cardio-renal syndromeand sudden death. Since the reduction of afferent neural signalscontributes to the systemic reduction of sympathetic tone/drive, renaldenervation might also be useful in treating other conditions associatedwith systemic sympathetic hyperactivity. Accordingly, renal denervationcan also benefit other organs and bodily structures innervated bysympathetic nerves, including those identified in FIG. 1. For example, areduction in central sympathetic drive may reduce the insulin resistancethat afflicts people with metabolic syndrome and Type II diabetics.Additionally, patients with osteoporosis are also sympatheticallyactivated and might also benefit from the downregulation of sympatheticdrive that accompanies renal denervation.

C. Achieving Intravascular Access to the Renal Artery

In accordance with the present invention, neuromodulation of a leftand/or right renal plexus (RP), which is intimately associated with aleft and/or right renal artery, may be achieved through intravascularaccess. As FIG. 4A shows, blood moved by contractions of the heart isconveyed from the left ventricle of the heart by the aorta. The aortadescends through the thorax and branches into the left and right renalarteries. Below the renal arteries, the aorta bifurcates at the left andright iliac arteries. The left and right iliac arteries descend,respectively, through the left and right legs and join the left andright femoral arteries.

As FIG. 4B shows, the blood collects in veins and returns to the heart,through the femoral veins into the iliac veins and into the inferiorvena cava. The inferior vena cava branches into the left and right renalveins. Above the renal veins, the inferior vena cava ascends to conveyblood into the right atrium of the heart. From the right atrium, theblood is pumped through the right ventricle into the lungs, where it isoxygenated. From the lungs, the oxygenated blood is conveyed into theleft atrium. From the left atrium, the oxygenated blood is conveyed bythe left ventricle back to the aorta.

As will be described in greater detail later, the femoral artery can beexposed and cannulated at the base of the femoral triangle, justinferior to the midpoint of the inguinal ligament. A catheter can beinserted through this access site, percutaneously into the femoralartery and passed into the iliac artery and aorta, into either the leftor right renal artery. This comprises an intravascular path that offersminimally invasive access to a respective renal artery and/or otherrenal blood vessels.

The wrist, upper arm, and shoulder region provide other locations forintroduction of catheters into the arterial system. Catheterization ofeither the radial, brachial, or axillary artery may be utilized inselect cases. Catheters introduced via these access points may be passedthrough the subclavian artery on the left side (or via the subclavianand brachiocephalic arteries on the right side), through the aorticarch, down the descending aorta and into the renal arteries usingstandard angiographic technique.

D. Properties and Characteristics of the Renal Vasculature

Since neuromodulation of a left and/or right renal plexus (RP) may beachieved in accordance with the present invention through intravascularaccess, properties and characteristics of the renal vasculature mayimpose constraints upon and/or inform the design of apparatus, systemsand methods for achieving such renal neuromodulation. Some of theseproperties and characteristics may vary across the patient populationand/or within a specific patient across time, as well as in response todisease states, such as hypertension, chronic kidney disease, vasculardisease, end-stage renal disease, insulin resistance, diabetes,metabolic syndrome, etc. These properties and characteristics, asexplained below, may have bearing on the clinical safety and efficacy ofthe procedure and the specific design of the intravascular device.Properties of interest may include, for example, material/mechanical,spatial, fluid dynamic/hemodynamic and/or thermodynamic properties.

As discussed previously, a catheter can be advanced percutaneously intoeither the left or right renal artery via a minimally invasiveintravascular path. However, minimally invasive renal arterial accesscan be challenging, for example, because, as compared to some otherarteries that are routinely accessed using catheters, the renal arteriesare often extremely tortuous, may be of relatively small diameter and/ormay be of relatively short length. Furthermore, renal arterialatherosclerosis is common in many patients, particularly those withcardiovascular disease. Renal arterial anatomy also may varysignificantly from patient to patient, further complicating minimallyinvasive access. Significant inter-patient variation may be seen, forexample, in relative tortuosity, diameter, length and/or atheroscleroticplaque burden, as well as in the take-off angle at which a renal arterybranches from the aorta. Apparatus, systems and methods for achievingrenal neuromodulation via intravascular access must account for theseand other aspects of renal arterial anatomy and its variation across thepatient population when minimally invasively accessing a renal artery.

In addition to complicating renal arterial access, specifics of therenal anatomy also complicate establishment of stable contact betweenneuromodulatory apparatus and a luminal surface or wall of a renalartery. When the neuromodulatory apparatus comprises an energy deliveryelement, such as an electrode, consistent positioning and contact forceapplication between the energy delivery element and the vessel wall isimportant for predictability and safety. However, navigation is impededby the tight space within a renal artery, as well as tortuosity of theartery. Furthermore, respiration and/or the cardiac cycle may causesignificant movement of the renal artery relative to the aorta, and thecardiac cycle and/or the neuromodulatory apparatus may transientlydistend the renal artery, further complicating establishment of stablecontact.

Even after accessing a renal artery and facilitating stable contactbetween neuromodulatory apparatus and a luminal surface of the artery,nerves in and around the adventia of the artery must be safely modulatedvia the neuromodulatory apparatus. Safely applying thermal treatmentfrom within a renal artery is non-trivial given the potential clinicalcomplications associated with such treatment. For example, the intimaand media of the renal artery are highly vulnerable to thermal injury.As discussed in greater detail below, the Intima-Media Thicknessseparating the vessel lumen from its adventitia means that target renalnerves may be multiple millimeters distant from the luminal surface ofthe artery. Sufficient thermal energy must be delivered to the targetrenal nerves to modulate the target renal nerves without excessivelyheating and desiccating the vessel wall. Another potential clinicalcomplication associated with excessive heating is thrombus formationfrom coagulating blood flowing through the artery. Given that thisthrombus can cause a kidney infarct, thereby causing irreversible damageto the kidney, thermal treatment from within the renal artery must beapplied carefully. Accordingly, the complex fluid mechanic andthermodynamic conditions present in the renal artery during treatment,particularly those that may impact heat transfer dynamics at thetreatment site, can be important is applying thermal treatment fromwithin the renal artery.

It is also desirable for the neuromodulatory apparatus to be configuredto allow for adjustable positioning and repositioning of the energydelivery element within the renal artery since location of treatment mayalso impact clinical safety and efficacy. For example, it may betempting to apply a full circumferential treatment from within the renalartery given that the renal nerves may be spaced circumferentiallyaround a renal artery. However, the full-circle lesion likely resultingfrom a continuous circumferential treatment may create a heighten riskof renal artery stenosis, thereby negating any potential therapeuticbenefit of the renal neuromodulation. Therefore, the formation of morecomplex lesions along a longitudinal dimension of the renal arteryand/or repositioning of the neuromodulatory apparatus to multipletreatment locations may be desirable. Additionally, variable positioningand repositioning of the neuromodulatory apparatus may prove to beuseful in circumstances where the renal artery is particularly tortuousor where there are proximal branch vessels off the renal artery mainvessel, making treatment in certain locations challenging.

Based on the above described challenges of (1) renal arteryintervention, (2) consistent and stable placement of the energy deliveryelement against the vessel wall, (3) safe application of thermaltreatment across the vessel wall, and (4) positioning and repositioningthe treatment apparatus to allow for multiple treatment locations,various independent and dependent properties of the renal vasculaturethat may be of interest include, for example, vessel diameter, length,intima-media thickness, coefficient of friction and tortuosity;distensibility, stiffness and modulus of elasticity of the vessel wall;peak systolic and end-diastolic blood flow velocity, as well as the meansystolic-diastolic peak blood flow velocity, mean/max volumetric bloodflow rate; specific heat capacity of blood and/or of the vessel wall,thermal conductivity of blood and/or of the vessel wall, thermalconvectivity of blood flow past a vessel wall treatment site and/orradiative heat transfer; and renal motion relative to the aorta, inducedby respiration and/or blood flow pulsatility, as well as the take-offangle of a renal artery relative to the aorta. These properties will bediscussed in greater detail with respect to the renal arteries. However,dependent on the apparatus, systems and methods utilized to achieverenal neuromodulation, such properties of the renal veins also may guideand/or constrain design characteristics.

Apparatus positioned within a renal artery must conform to the geometryof the artery. Renal artery vessel diameter, D_(RA), typically is in arange of about 2-10 mm, with an average of about 6 mm. Renal arteryvessel length, L_(RA), between its ostium at the aorta/renal arteryjuncture and its distal branchings, generally is in a range of about5-70 mm, more generally in a range of about 20-50 mm. Since the targetrenal plexus is embedded within the adventitia of the renal artery, thecomposite Intima-Media Thickness, IMT, (i.e., the radial outwarddistance from the artery's luminal surface to the adventitia containingtarget neural structures) also is notable and generally is in a range ofabout 0.5-2.5 mm, with an average of about 1.5 mm. Although a certaindepth of treatment is important to reach the target neural fibers, thetreatment should not be too deep (e.g., >5 mm from inner wall of therenal artery) to avoid non-target tissue and anatomical structures suchas the renal vein.

Apparatus navigated within a renal artery also must contend withfriction and tortuosity. The coefficient of friction, μ, (e.g., staticor kinetic friction) at the wall of a renal artery generally is quitelow, for example, generally is less than about 0.05, or less than about0.03. Tortuosity, τ, a measure of the relative twistiness of a curvedsegment, has been quantified in various ways. The arc-chord ratiodefines tortuosity as the length of a curve, L_(curve), divided by thechord, C_(curve), connecting the ends of the curve (i.e., the lineardistance separating the ends of the curve):

τ=L _(curve) /C _(curve)  (1)

Renal artery tortuosity, as defined by the arc-chord ratio, is generallyin the range of about 1-2.

The pressure change between diastole and systole changes the luminaldiameter of the renal artery, providing information on the bulk materialproperties of the vessel. The Distensibility Coefficient, DC, a propertydependent on actual blood pressure, captures the relationship betweenpulse pressure and diameter change:

DC=2*((D _(sys) −D _(dia))/D _(dia))/ΔP=2*(ΔD/D _(cha))/ΔP,  (2)

where D_(sys) is the systolic diameter of the renal artery, D_(dia) isthe diastolic diameter of the renal artery, and AD (which generally isless than about 1 mm, e.g., in the range of about 0.1 mm to 1 mm) is thedifference between the two diameters:

ΔD=D _(sys) −D _(dia)  (3)

The renal arterial Distensibility Coefficient is generally in the rangeof about 20-50 kPa⁻¹*10⁻³.

The luminal diameter change during the cardiac cycle also may be used todetermine renal arterial Stiffness, β. Unlike the DistensibilityCoefficient, Stiffness is a dimensionless property and is independent ofactual blood pressure in normotensive patients:

β=(ln [BP _(sys) /BP _(dia)])/(ΔD/D _(dia))  (4)

Renal arterial Stiffness generally is in the range of about 3.5-4.5.

In combination with other geometric properties of the renal artery, theDistensibility Coefficient may be utilized to determine the renalartery's Incremental Modulus of Elasticity, E_(inc):

E _(inc)=3(1+(LCSA/IMCSA))/DC,  (5)

where LCSA is the luminal cross-sectional area and IMCSA is theintima-media cross-sectional area:

LCSA=π(D _(dia)/2)²  (6)

IMCSA=π(D _(dia)/2+IMT)²−LCSA  (7)

For the renal artery, LCSA is in the range of about 7-50 mm², IMCSA isin the range of about 5-80 mm², and E_(inc) is in the range of about0.1-0.4 kPa*10 ³.

For patients without significant Renal Arterial Stenosis (RAS), peakrenal artery systolic blood flow velocity, υ_(max-sys), generally isless than about 200 cm/s; while peak renal artery end-diastolic bloodflow velocity, υ_(max-dia), generally is less than about 150 cm/s, e.g.,about 120 cm/s.

In addition to the blood flow velocity profile of a renal artery,volumetric flow rate also is of interest. Assuming Poiseulle flow, thevolumetric flow rate through a tube, Φ, (often measured at the outlet ofthe tube) is defined as the average velocity of fluid flow through thetube, υ_(avg), times the cross-sectional area of the tube:

Φ=υ_(avg) *πR ²  (8)

By integrating the velocity profile (defined in Eq. 10 above) over all rfrom 0 to R, it can be shown that:

Φ=υ_(avg) *πR ²=(πR ⁴ *ΔPr)/8ηΔx  (9)

As discussed previously, for the purposes of the renal artery, η may bedefined as η_(blood), Δx may be defined as L_(RA), and R may be definedas D_(RA)/2. The change in pressure, ΔPr, across the renal artery may bemeasured at a common point in the cardiac cycle (e.g., via apressure-sensing guidewire) to determine the volumetric flow ratethrough the renal artery at the chosen common point in the cardiac cycle(e.g. during systole and/or during enddiastole). Volumetric flow rateadditionally or alternatively may be measured directly or may bedetermined from blood flow velocity measurements. The volumetric bloodflow rate through a renal artery generally is in the range of about500-1000 mL/min.

Thermodynamic properties of the renal artery also are of interest. Suchproperties include, for example, the specific heat capacity of bloodand/or of the vessel wall, thermal conductivity of blood and/or of thevessel wall, thermal convectivity of blood flow past a vessel walltreatment site. Thermal radiation also may be of interest, but it isexpected that the magnitude of conductive and/or convective heattransfer is significantly higher than the magnitude of radiative heattransfer.

The heat transfer coefficient may be empirically measured, or may becalculated as a function of the thermal conductivity, the vesseldiameter and the Nusselt Number. The Nusselt Number is a function of theReynolds Number and the Prandtl Number. Calculation of the ReynoldsNumber takes into account flow velocity and rate, as well as fluidviscosity and density, while calculation of the Prandtl Number takesinto account specific heat, as well as fluid viscosity and thermalconductivity. The heat transfer coefficient of blood flowing through therenal artery is generally in the range of about 500-6000 W/m²K.

An additional property of the renal artery that may be of interest isthe degree of renal motion relative to the aorta, induced by respirationand/or blood flow pulsatility. A patient's kidney, located at the distalend of the renal artery, can move as much as 5 cm cranially withrespiratory excursion. This may impart significant motion to the renalartery connecting the aorta and the kidney, thereby requiring from theneuromodulatory apparatus a unique balance of stiffness and flexibilityto maintain contact between the thermal treatment element and the vesselwall during cycles of respiration. Furthermore, the take-off anglebetween the renal artery and the aorta may vary significantly betweenpatients, and also may vary dynamically within a patient, e.g., due tokidney motion. The take-off angle generally may be in a range of about30°-135°.

These and other properties of the renal vasculature may imposeconstraints upon and/or inform the design of apparatus, systems andmethods for achieving renal neuromodulation via intravascular access.Specific design requirements may include accessing the renal artery,facilitating stable contact between neuromodulatory apparatus and aluminal surface or wall of the renal artery, and/or safely modulatingthe renal nerves with the neuromodulatory apparatus.

II. CATHETER APPARATUSES, SYSTEMS AND METHODS FOR RENAL NEUROMODULATIONA. Overview

FIG. 5 shows a system 10 for thermally inducing neuromodulation of aleft and/or right renal plexus (RP) through intravascular access.

As just described, the left and/or right renal plexus (RP) surrounds therespective left and/or right renal artery. The renal plexus (RP) extendsin intimate association with the respective renal artery into thesubstance of the kidney. The system thermally induces neuromodulation ofa renal plexus (RP) by intravascular access into the respective left orright renal artery.

The system 10 includes an intravascular treatment device 12. Thetreatment device 12 provides access to the renal plexus (RP) through anintravascular path 14 that leads to a respective renal artery, as FIG.6A shows.

As FIG. 5 shows, the treatment device 12 includes an elongated shaft 16having a proximal end region 18 and a distal end region 20.

The proximal end region 18 of the elongated shaft 16 is optionallyconnected to a handle assembly 200. The handle assembly 200 is sized andconfigured to be securely or ergonomically held and manipulated by acaregiver (see, e.g., FIG. 17A) outside an intravascular path 14 (see,e.g., FIG. 6A). By manipulating the handle assembly 200 from outside theintravascular path 14, the caregiver can advance the elongated shaft 16through the tortuous intravascular path 14 and remotely manipulate oractuate the distal end region 20. Image guidance, e.g., CT,radiographic, IVUS, OCT or another suitable guidance modality, orcombinations thereof, can be used to aid the caregiver's manipulation.

As shown in FIG. 6B, the distal end region 20 of the elongated shaft 16can flex in a substantial fashion to gain entrance into a respectiveleft/right renal artery by manipulation of the elongated shaft 16. Asshown in FIGS. 24A and 24B, the distal end region 20 of the elongatedshaft 16 can gain entrance to the renal artery via passage within aguide catheter 94. The distal end region 20 of the elongated shaft 16carries at least one energy delivery element 24 (e.g., radiofrequencyelectrode, electrode, cooled radiofrequency electrode, thermal element,thermal heating element, electrically resistive heating element,cryoablation applicator, microwave antenna, ultrasound transducer, highintensity focused ultrasound transducer, laser emitter). The energydelivery element 24 is also specially sized and configured formanipulation and use within a renal artery.

As FIG. 6B shows (and as will be described in greater detail later),once entrance to a renal artery is gained, further manipulation of thedistal end region 20 and the energy delivery element 24 within therespective renal artery establishes proximity to and alignment betweenthe energy delivery element(s) 24 and tissue along an interior wall ofthe respective renal artery. In some embodiments, manipulation of thedistal end region 20 will also facilitate contact between the energydelivery element 24 and a wall of the renal artery. In the context ofthe present application, the phrasing “contact between an energydelivery element and a wall of the renal artery” generally meanscontiguous physical contact with or without atraumatic distension of therenal artery wall and without puncturing or perforating the renal arterywall.

As also will be described in greater detail later, different sections ofthe elongated shaft 16 serve different mechanical functions when in use.The sections are thereby desirably differentiated in terms of theirsize, configuration and mechanical properties for (i) percutaneousintroduction into a femoral artery through a small-diameter access site;(ii) atraumatic passage through the tortuous intravascular path 14through an iliac artery, into the aorta, and into a respectiveleft/right renal artery, including (iii) significant flexure near thejunction of the left/right renal arteries and aorta to gain entry intothe respective left or right renal artery; (iv) controlled translation,deflection, rotation and/or actuation within the respective renal arteryto attain proximity to and a desired alignment with an interior wall ofthe respective renal artery; (v) the placement of at least one energydelivery element 24 into contact with tissue on the interior wall; (vi)allowing substantially stable contact force between the at least oneenergy delivery element and the interior wall during motion of the renalartery with respect to the aorta due to respiration and/or blood flowpulsatility; and (vii) repositioning via retraction and/or rotationwithin the renal artery for subsequent treatment(s).

Referring back to FIG. 5, the system 10 also includes an energygenerator 26 (e.g., a radiofrequency generator). Under the control ofthe caregiver or automated control algorithm 102 (as will be describedin greater detail later), the generator 26 generates a selected form andmagnitude of energy. A cable 28 operatively attached to the handleassembly 200 electrically connects the energy delivery element 24 to thegenerator 26. At least one supply wire (not shown) passing along theelongated shaft 16 or through a lumen in the elongated shaft 16 from thehandle assembly 200 to the energy delivery element 24 conveys thetreatment energy to the energy delivery element 24. A control mechanism,such as foot pedal 100, can be connected (e.g., pneumatically connectedor electrically connected) to the generator 26 to allow the operator toinitiate, terminate and, optionally, adjust various operationalcharacteristics of the generator, including, but not limited to, powerdelivery.

For systems that provide for the delivery of a monopolar electric fieldvia the energy delivery element 24, a neutral or dispersive electrode 38can be electrically connected to the generator 26 and attached to theexterior of the patient. Additionally, one or more sensors 52 (see,e.g., FIGS. 12 and 24), such as one or more temperature (e.g.,thermocouple, thermistor, etc.), impedance, pressure, optical, flow,chemical or other sensors, can be located proximate to or within theenergy delivery element and connected to one or more of the supplywires. For example, a total of two supply wires can be included, inwhich both wires could transmit the signal from the sensor and one wirecould serve dual purpose and also convey the energy to the energydelivery element. Alternatively, both wires could transmit energy to theenergy delivery element.

Once proximity between, alignment with, and contact between the energydelivery element 24 and tissue are established within the respectiverenal artery (as FIG. 6B shows), the purposeful application of energyfrom the generator 26 to tissue by the energy delivery element 24induces one or more desired neuromodulating effects on localized regionsof the renal artery and adjacent regions of the renal plexus (RP), whichlay intimately within or adjacent to the adventitia of the renal artery.The purposeful application of the neuromodulating effects can achieveneuromodulation along all or a portion of the RP.

The neuromodulating effects can include thermal ablation, non-ablativethermal alteration or damage (e.g., via sustained heating and/orresistive heating), and electromagnetic neuromodulation. Desired thermalheating effects may include raising the temperature of target neuralfibers above a desired threshold to achieve non-ablative thermalalteration, or above a higher temperature to achieve ablative thermalalteration. For example, the target temperature can be above bodytemperature (e.g., approximately 37° C.) but less than about 45° C. fornon-ablative thermal alteration, or the target temperature can be about45° C. or higher for the ablative thermal alteration. Desiredelectromagnetic neuromodulation effects may include altering theelectrical signals transmitted in a nerve.

Further details of special size, configuration, and mechanicalproperties of the elongated shaft 16, the distal end region 20 and theenergy delivery element 24, as well as other aspects of the system 10,will now be described. In still other embodiments, the system 10 mayhave a different configuration and/or include different features. Forexample, alternative multi-energy delivery element devices, such asmulti-electrode baskets, spirals or lassos, or balloon expandabledevices, may be implemented to intravascularly deliver neuromodulatorytreatment with or without contacting the vessel wall.

B. Size and Configuration of the Elongated Shaft for AchievingIntravascular Access to a Renal Artery

As explained above, intravascular access to an interior of a renalartery can be achieved, for example, through the femoral artery. As FIG.6A shows, the elongated shaft 16 is specially sized and configured toaccommodate passage through this intravascular path 14, which leads froma percutaneous access site in the femoral artery to a targeted treatmentsite within a renal artery. In this way, the caregiver is able to orientthe energy delivery element 24 within the renal artery for its intendedpurpose.

For practical purposes, the maximum outer dimension (e.g., diameter) ofany section of the elongated shaft 16, including the energy deliveryelement 24 it carries, is dictated by the inner diameter of the guidecatheter or delivery catheter through which the elongated shaft 16 ispassed. Assuming, for example, that an 8 French guide catheter (whichhas an inner diameter of approximately 0.091 inches) would likely be,from a clinical perspective, the largest guide catheter used to accessthe renal artery, and allowing for a reasonable clearance tolerancebetween the energy delivery element 24 and the guide catheter, themaximum outer dimension can be realistically expressed as being lessthan or equal to approximately 0.085 inches. However, use of a smaller 5French guide catheter 94 may require the use of smaller outer diametersalong the elongated shaft 16. For example, an energy delivery element 24that is to be routed within a 5 French guide catheter would have anouter dimension of no greater than 0.053 inches. In another example, anenergy delivery element 24 that is to be routed within a 6 French guidecatheter would have an outer dimension of no greater than 0.070 inches.

1. Force Transmitting Section

As FIG. 7A shows, the proximal end region 18 of the elongated shaft 16includes, coupled to the handle assembly 200, a force transmittingsection 30. The force transmitting section 30 is sized and configured topossess selected mechanical properties that accommodate physical passagethrough and the transmission of forces within the intravascular path 14,as it leads from the accessed femoral artery (left or right), throughthe respective iliac branch artery and into the aorta, and in proximityto the targeted renal artery (left or right). The mechanical propertiesof the force transmitting section 30 include at least a preferredeffective length (expressed in inches or centimeters). It should beunderstood that the term force transmitting section can be usedinterchangeably with elongated tubular shaft or proximal forcetransmitting section.

As FIG. 7A shows, the force transmitting section 30 includes a preferredeffective length L1. The preferred effective length L1 is a function ofthe anatomic distance within the intravascular path 14 between theaccess site and a location proximate to the junction of the aorta andrenal arteries. The preferred effective length L1 can be derived fromtextbooks of human anatomy, augmented by a caregiver's knowledge of thetargeted site generally or as derived from prior analysis of theparticular morphology of the targeted site. The preferred effectivelength L1 is also dependent on the length of the guide catheter that isused, if any. In a representative embodiment, for a normal human, thepreferred effective length L1 comprises about 30 cm to about 110 cm. Ifno guide catheter is used, then the preferred effective length L1comprises about 30 cm to about 35 cm. If a 55 cm length guide catheteris used, then the preferred effective length L1 comprises about 65 cm toabout 70 cm. If a 90 cm length guide catheter is used, then thepreferred effective length L1 comprises about 95 cm to about 105 cm.

The force transmitting section 30 also includes a preferred axialstiffness and a preferred torsional stiffness. The preferred axialstiffness expresses the capability of the force transmitting section 30to be advanced or withdrawn along the length of the intravascular path14 without buckling or substantial deformation. Since some axialdeformation is necessary for the force transmitting section 30 tonavigate the tortuous intravascular path 14 without providing too muchresistance, the preferred axial stiffness of the force transmittingsection should also provide this capability. The preferred torsionalstiffness expresses the capability of the force transmitting section 30to rotate the elongated shaft 16 about its longitudinal axis along itslength without kinking or permanent deformation. As will be described ingreater detail later, the ability to advance and retract, as well asrotate, the distal end region 20 of the elongated shaft 16 within therespective renal artery is desirable.

The desired magnitude of axial stiffness and rotational stiffness forthe force transmitting section 30 can be obtained by selection ofconstituent material or materials to provide a desired elastic modulus(expressed in terms, e.g., of a Young's Modulus (E)) indicative of axialand torsional stiffnesses, as well as selecting the construct andconfiguration of the force transmitted section in terms of, e.g., itsinterior diameter, outer diameter, wall thickness, and structuralfeatures, including cross-sectional dimensions and geometry.Representative examples are described in greater detail below.

2. First Flexure Zone

As FIGS. 7A and 7B show, the distal end region 20 of the elongated shaft16 is coupled to the force transmitting section 30. The length L1 of theforce transmitting section 30 generally serves to bring the distal endregion 20 into the vicinity of the junction of the respective renalartery and aorta (as FIG. 6B shows). The axial stiffness and torsionalstiffness of the force transmitting region transfer axial and rotationforces from the handle assembly 200 to the distal end region 20, as willbe described in greater detail later. It should be understood that theterm first flexure zone can be used interchangeably with flexibletubular structure.

As shown in FIG. 7B, the distal end region 20 includes a first flexurezone 32 proximate to the force transmitting section 30. The firstflexure zone 32 is sized and configured to have mechanical propertiesthat accommodate significant flexure or bending at a prescribedpreferred access angle α1 and provide for the transmission of torqueduring rotation, without fracture, collapse, substantial distortion, orsignificant twisting of the elongated shaft 16. The first flexure zone32 should accommodate flexure sufficient for the distal end region 20 toadvance via a guide catheter into the renal artery without substantiallystraightening out the guide catheter.

Angle α1 is defined by the angular deviation that the treatment device12 must navigate to transition between the aorta (along which the forcetransmitting section 30 is aligned) and the targeted renal artery (alongwhich the distal end region 20 is aligned) (this is also shown in FIG.6B). This is the angle that the first flexure zone 32 must approximateto align the distal end region 20 of the elongated shaft 16 with thetargeted renal artery, while the force transmitting section 30 of theelongated shaft 16 remains aligned with the native axis of the aorta (asFIG. 6B shows). The more severe the take-off angle between the renalartery and the aorta, the greater bend the first flexure zone 32 willneed to make for the distal end region of the treatment device to accessthe renal artery and the smaller the angle α1.

When the catheter is outside the patient and the first flexure zone 32is in a substantially straight, non-deflected configuration, angle α1(as shown in FIG. 7B) is approximately 180°. Upon full deflection of thefirst flexure zone 32, the angle α1 is reduced to anywhere between about30° and 180°. In a representative embodiment, upon full deflection angleα1 is about 30° to about 135°. In another representative embodiment,upon full deflection angle α1 is about 90°.

The first flexure zone 32 is sized and configured to possess mechanicalproperties that accommodate significant, abrupt flexure or bending atthe access angle α1 near the junction of the aorta and the renal artery.Due to its size, configuration, and mechanical properties, the firstflexure zone 32 must resolve these flexure or bending forces withoutfracture, collapse, distortion, or significant twisting. Such flexure orbending of the first flexure zone may occur at least in part within thedistal region of a guide catheter without substantially straighteningout the guide catheter. The resolution of these flexure or bendingforces by the first flexure zone 32 makes it possible for the distal endregion 20 of the elongated shaft 16 to gain entry along theintravascular path 14 into a targeted left or right renal artery.

The first flexure zone 32 is sized and configured in length L2 to beless than length L1 (see FIG. 7A). That is because the distance betweenthe femoral access site and the junction of the aorta and renal artery(typically approximating about 40 cm to about 55 cm) is generallygreater than the length of a renal artery between the aorta and the mostdistal treatment site along the length of the renal artery, which istypically less than about 7 cm. The preferred effective length L2 can bederived from textbooks of human anatomy, augmented with a caregiver'sknowledge of the site generally or as derived from prior analysis of theparticular morphology of the targeted site. For example, the length L2generally may be less than about 15 cm, e.g., may be less than about 10cm. In one representative embodiment, the length L2 may be about 9 cm.

Desirably, the length L2 is selected to make it possible to rest aportion of the first flexure zone 32 partially in the aorta at or nearthe length L1, as well as rest the remaining portion of the firstflexure zone 32 partially within the renal artery (as FIG. 6B shows). Inthis way, the first flexure zone 32 defines a transitional bend that issupported and stable within the vasculature.

In the deflected configuration of FIG. 7B, the first flexure zone 32comprises a radius of curvature RoC₁. In embodiments where the curvatureof first flexure zone 32 does not vary or is consistent along the lengthL2, the length L2 and the deflection angle α1 may define the radius ofcurvature RoC₁. It should be understood that the curvature of firstflexure zone 32, and thereby the radius of curvature RoC₁ of the firstflexure zone, alternatively may vary along the length L2.

In such embodiments where the curvature does not vary, the length L2 maydefine a fraction (180°−α1)/360° of the circumference C₁ of a circlewith an equivalent radius of curvature RoC₁. Thus, the circumference ofsuch an equivalent circle is:

$\begin{matrix}{C_{1} = {{\frac{360{^\circ}}{\left( {{180{^\circ}} - {\alpha \; 1}} \right)} \times L\; 2} = {2\pi \times {RoC}_{1}}}} & (10)\end{matrix}$

Solving for the radius of curvature RoC₁:

$\begin{matrix}{{RoC}_{1} = \frac{360{^\circ} \times L\; 2}{2\pi \times \left( {{180{^\circ}} - {\alpha \; 1}} \right)}} & (11)\end{matrix}$

Thus, in a representative embodiment of the first flexure zone 32 wherethe curvature of the first flexure zone does not vary along the lengthL2, where the length L2 is about 9 cm, and where the angle α1 is about30° to about 135°, the radius of curvature RoC₁ is about 3.5 cm to about11.5 cm. In a representative embodiment of first flexure zone 32 wherethe curvature of the first flexure zone does not vary along the lengthL2, where the length L2 is about 9 cm, and where the angle α1 is about90°, the radius of curvature RoC₁ is about 5.75 cm.

As will be apparent, Equation (11) may be rearranged such that thelength L2 and the radius of curvature RoC₁ define the angle α1.Furthermore, Equation (11) may be rearranged such that the radius ofcurvature RoC₁ and the angle α1 define the length L2. Thus, inembodiments where the curvature of first flexure zone 34 does not varyalong the length L2, any one of the length L2, angle α1 and radius ofcurvature RoC₁ may be specified by specifying the other two variables.

As will be described in greater detail later, and as shown in FIG. 6B,the length L2 of the first flexure zone 32 optionally does not extendthe full length of the targeted length of the renal artery. That isbecause the distal end region 20 of the elongated shaft 16 optionallyincludes one or more additional flexure zones, distal to the firstflexure zone 32 (toward the substance of the kidney), to accommodateother different functions important to the therapeutic objectives of thetreatment device 12. As will be described later, the ability to transmittorque through the first flexure zone 32 makes it possible to rotate thethermal heating device to properly position the energy delivery elementwithin the renal artery for treatment.

In terms of axial and torsional stiffness, the mechanical properties offirst flexure zone 32 can, and desirably do, differ from the mechanicalproperties of the force transmitting section 30. This is because thefirst flexure zone 32 and the force transmitting section serve differentfunctions while in use. Alternatively, the mechanical properties offirst flexure zone 32 and force transmitting section 30 can be similar.

The force transmitting section 30 serves in use to transmit axial loadand torque over a relatively long length (L1) within the vascularpathway. In contrast, the first flexure zone 32 needs to transmit axialload and torque over a lesser length L2 proximate to or within arespective renal artery. Importantly, the first flexure zone 32 mustabruptly conform to an access angle α1 near the junction of the aortaand the respective renal artery, without fracture, collapse, significanttwisting, or straightening a guide catheter imparting the access angleα1. This is a function that the force transmitting zone need notperform. Accordingly, the first flexure zone 32 is sized and configuredto be less stiff and to possess greater flexibility than the forcetransmitting section 30.

Additionally, the first flexure zone 32 may allow energy deliveryelement(s) 24 to maintain stable contact with the interior wall of therenal artery as the respective kidney moves due to patient respiration.As a patient breathes the kidney may move, causing the renal artery topivot about the ostium, where the renal artery joins the aorta. Stablecontact between the energy delivery element(s) 24 and the inner wall ofthe renal artery is desired during energy delivery. Therefore, theenergy delivery element(s) 24 must move, along with the renal artery,relative to the aorta. The mechanical properties of the first flexurezone 32 that accommodate significant, abrupt flexure or bending at theaccess angle α1 near the junction of the aorta and the renal artery alsoallow the sections of the catheter distal to the first flexure zone 32to pivot about the ostium without significant impediment, allowing theenergy delivery element to maintain stable contact force with the innerwall of the renal artery. In some embodiments, deflectable section 34distal to first flexure zone 32 may become more stiff than the firstflexure zone 32 when it is controllably deflected. The additionalstiffness of deflectable section 34 helps maintain a stable contactforce between the energy delivery element 24 and an inner wall of therenal artery and allows the catheter to move with the renal arteryrelative to the aorta with sufficient freedom due to the flexibledeformation of the first flexure zone 32. The renal artery pivots aboutthe juncture with the aorta such that movement of the renal arteryincreases with distance from the juncture with the aorta. The length ofthe distal end region 20 distal to the first flexure zone 32 along withthe length of the first flexure zone 32 is configured such that anincreasing portion of the first flexure zone 32 is positioned in therenal artery the more distal the treatment site to provide sufficientincreased flexibility in the region of the juncture with the aorta toallow stable contact force between the energy delivery element 24 andthe more distal treatment site of the inner wall of the renal artery,especially during increased motion at the more distal treatment site.

The desired magnitude of axial stiffness, rotational stiffness, andflexibility for the first flexure zone 32 can be obtained by selectionof constituent material or materials to provide a desired elasticmodulus (expressed, e.g., in terms of a Young's Modulus (E)) indicativeof flexibility, as well as selecting the construct and configuration ofthe force transmitting section, e.g., in terms of its interior diameter,outer diameter, wall thickness, and structural features, includingcross-sectional dimensions and geometry. Representative examples will bedescribed in greater detail later.

Although it is desirable that the force transmitting section 30 and thefirst flexure zone 32 have stiffness and flexibility properties that areunique to their respective functions, it is possible that the forcetransmitting section 30 and the first flexure zone 32 comprise the samematerials, size and geometric configuration such that the forcetransmitting section 30 and the first flexure zone 32 constitute thesame section.

3. Deflectable Section

As shown in FIGS. 7A, 7B, and 7C, the distal end region 20 of theelongated shaft 16 also optionally may include, distal to the firstflexure zone 32, a deflectable section 34. In some embodiments, theenergy delivery element 24 may be supported by the deflectable section34. It should be understood that the deflectable section can be usedinterchangeably with second flexure zone or intermediate flexure zone ordeflectable tubular body.

The deflectable section 34 is sized, configured, and has the mechanicalproperties that accommodate additional flexure or bending, independentof the first flexure zone 32, at a preferred contact angle α2, withoutfracture, collapse, substantial distortion, or significant twisting. Thedeflectable section 34 should also accommodate flexure sufficient forthe distal end region 20 to advance via a guide catheter into the renalartery without straightening out the guide catheter.

The preferred contact angle α2 is defined by the angle through which theenergy delivery element 24 can be radially deflected within the renalartery to establish contact between the energy delivery element 24 andan inner wall of the respective renal artery (as FIG. 6B shows). Themagnitude of the contact angle α2 and the length of the deflectablesection L3 preferably are based on the native inside diameter of therespective renal artery where the energy delivery element 24 rests,which may vary between about 2 mm and about 10 mm, as well as thediameter of the energy delivery element 24. It is most common for thediameter of the renal artery to vary between about 2 mm and about 8 mm,with a mean diameter of about 6 mm.

The deflectable section 34 extends distally from the first flexure zone32 for a length L3 into the targeted renal artery (see FIG. 6B).Desirably, the length L3 is selected, taking into account the length L2of the first flexure zone 32 that extends into the renal artery, as wellas the anatomy of the respective renal artery, to actively place theenergy delivery element 24 (carried at the end of the distal end region20) at or near the targeted treatment site (as FIG. 6B shows). Thelength L3 can be derived, taking the length L2 into account, fromtextbooks of human anatomy, together with a caregiver's knowledge of thesite generally or as derived from prior analysis of the particularmorphology of the targeted site.

As FIG. 7A shows, the deflectable section 34 is desirably sized andconfigured in length L3 to be less than length L2. This is because, interms of length, the distance required for actively deflecting theenergy delivery element 24 into contact with a wall of the renal arteryis significantly less than the distance required for bending theelongated shaft 16 to gain access from the aorta into the renal artery.Thus, the length of the renal artery is occupied in large part by thedeflectable section 34 and not as much by the first flexure zone 32.

In a representative embodiment, L2 is about 9 cm and L3 is about 5 mm toabout 15 mm. In certain embodiments, particularly for treatments inrelatively long blood vessels, L3 can be as long as about 20 mm. Inanother representative embodiment, and as described later in greaterdetail, L3 is about 12.5 mm.

When the catheter is outside the patient and the deflectable section 34is in a substantially straight, non-deflected configuration, contactangle α2 (as shown in FIG. 7C) is approximately 180°. Upon fulldeflection of the deflectable section 34, the angle α2 is reduced toanywhere between about 45° and 180°. In a representative embodiment,upon full deflection, angle α2 is about 75° to about 135°. In anotherrepresentative embodiment, upon full deflection, angle α2 is about 90°.

In the deflected configuration of FIG. 7C, the deflectable section 34comprises a radius of curvature RoC₂. In embodiments where the curvatureof deflectable section 34 does not vary or is consistent along thelength L3, the length L3 and the contact angle α2 may define the radiusof curvature RoC₂. It should be understood that the curvature ofdeflectable section 34, and thereby the radius of curvature RoC₂ of thedeflectable section, alternatively may vary along the length L3.

In such embodiments where the curvature does not vary, the length L3 maydefine a fraction (180°−α2)/360° of the circumference C₂ of a circlewith an equivalent radius of curvature RoC₂. Thus, the circumference ofsuch an equivalent circle is:

$\begin{matrix}{C_{2} = {{\frac{360{^\circ}}{\left( {{180{^\circ}} - {\alpha \; 2}} \right)} \times L\; 3} = {2\pi \times {RoC}_{2}}}} & (12)\end{matrix}$

Solving for the radius of curvature RoC₂:

$\begin{matrix}{{RoC}_{2} = \frac{360{^\circ} \times L\; 3}{2\pi \times \left( {{180{^\circ}} - {\alpha \; 2}} \right)}} & (13)\end{matrix}$

Thus, in a representative embodiment of the deflectable section 34 wherethe curvature of the deflectable section does not vary along the lengthL3, where the length L3 is about 5 mm to about 20 mm, and where thecontact angle α2 is about 75° to about 135°, the radius of curvatureRoC₂ is about 3 mm to about 25 mm. In a representative embodiment ofdeflectable section 34 where the curvature of the deflectable sectiondoes not vary along the length L3, where the length L3 is about 12.5 mm,for example less than or equal to about 12.5 mm, and where the angle α2is about 75° to about 135°, the radius of curvature RoC₂ is about 7 mmto about 16 mm, for example less than or equal to about 15 mm. In arepresentative embodiment of deflectable section 34 where the curvatureof the deflectable section does not vary along the length L3, where thelength L3 is about 12.5 mm, and where the angle α2 is about 90°, theradius of curvature RoC₂ is about 8 mm.

As will be apparent, Equation (13) may be rearranged such that thelength L3 and the radius of curvature RoC₂ define the contact angle α2.Furthermore, Equation (13) may be rearranged such that the radius ofcurvature RoC₂ and the angle α2 define the length L3. Thus, inembodiments where the curvature of deflectable section 34 does not varyalong the length L3, any one of the length L3, angle α2 and radius ofcurvature RoC₂ may be specified by specifying the other two variables.

In the deflected configuration of FIG. 7C, the deflectable section 34locates the energy delivery element 24 at a dimension Y from alongitudinal axis A of the deflectable section 34 just distal of thefirst flexure zone 32. The dimension Y can vary from about 2 mm to about20 mm. In some configurations, and given the dimension of most renalarteries, the dimension Y can be from about 5 mm to about 15 mm. Sincethe average diameter of most renal arteries is generally less than 10 mmas described below, it may be desirable for dimension Y to be less thanor equal to 10 mm. For example the Y dimension can be 6 mm or 8 mm oranywhere between and including 6 mm to 10 mm.

By way of example, the average diameter of a human renal artery is fromabout 2 mm to about 8 mm, but may range from about 2 mm to about 10 mm.Accordingly, if the distal end of the first flexure zone 32 werepositioned adjacent to a wall of an artery having an 8 mm diameter, thedeflectable section 34 would be capable of deflection sufficient for theenergy delivery element 24 to contact the opposite wall of the artery.In other embodiments, however, the dimension Y may have a differentvalue and may be oversized to facilitate contact in a straight or curvedvessel. The deflectable section 34 is also configured to locate theenergy delivery element 24 at a dimension X from a distal end of thefirst flexure zone 32. The dimension X can vary, e.g., based on thedimension Y and the length L3.

As FIG. 7C shows, having first flexure zone and deflectable section 32and 34, the distal end region 20 of the elongated shaft 16 can, in use,be placed into a complex, multi-bend structure 36. The complex,multi-bend structure 36 comprises one deflection region at the accessangle α1 over a length L2 (the first flexure zone 32) and a seconddeflection region at the contact angle α2 over a length L3 (thedeflectable section 34). In the complex, multi-bend, both L2 and L3 andangle α1 and angle α2 can differ. This is because the angle α1 andlength L2 are specially sized and configured to gain access from anaorta into a respective renal artery through a femoral artery accesspoint, and the angle α2 and length L3 are specially sized and configuredto align an energy delivery element 24 with an interior wall inside therenal artery.

In the illustrated embodiment (see, e.g., FIG. 7C), the deflectablesection 34 is sized and configured to allow a caregiver to remotelydeflect the deflectable section 34 within the renal artery, to radiallyposition the energy delivery element 24 into contact with an inner wallof the renal artery.

In the illustrated embodiment, a control mechanism is coupled to thedeflectable section 34. The control mechanism includes a control wire 40attached to the distal end of the deflectable section 34 (arepresentative embodiment is shown in FIGS. 15B and 15C and will bedescribed in greater detail later). It should be understood that theterm control wire can be used interchangeably with flexure controlelement. The control wire 40 is passed proximally through the elongatedshaft 16 and coupled to an actuator 260 on the handle assembly 200.Operation of the actuator 260 (e.g., by the caregiver pulling proximallyon or pushing forward the actuator 260) pulls the control wire 40 backto apply a compressive and bending force to the deflectable section 34(as FIGS. 7C and 15C show) resulting in bending. The compressive forcein combination with the optional directionally biased stiffness(described further below) of the deflectable section 34 deflects thedeflectable section 34 and, thereby, radially moves the energy deliveryelement 24 toward an interior wall of the renal artery (as FIG. 6Bshows).

Desirably, as will be described in greater detail later, the distal endregion 20 of the elongated shaft 16 can be sized and configured to varythe stiffness of the deflectable section 34 about its circumference. Thevariable circumferential stiffness imparts preferential and directionalbending to the deflectable section 34 (i.e., directionally biasedstiffness). In response to operation of the actuator 260, thedeflectable section 34 may be configured to bend in a singlepreferential direction. Representative embodiments exemplifying thisfeature will be described in greater detail later. Additionalrepresentative embodiments depicting multidirectional bending will alsobe described later in greater detail.

The compressive and bending force and resulting directional bending fromthe deflection of the deflectable section 34 has the consequence ofaltering the axial stiffness of the deflectable section. The actuationof the control wire 40 serves to increase the axial stiffness of thedeflectable section. As will be described later, the axial stiffness ofthe deflected deflectable section in combination with other flexibleaspects of the distal end region of the catheter treatment device allowsfor favorable performance in a renal artery neuromodulation treatment.

In terms of axial and torsional stiffnesses, the mechanical propertiesof deflectable section 34 can, and desirably do, differ from themechanical properties of the first flexure zone 32. This is because thefirst flexure zone 32 and the deflectable section 34 serve differentfunctions while in use.

The first flexure zone 32 transmits axial load and torque over a longerlength (L2) than the deflectable section 34 (L3). Importantly, thedeflectable section 34 is also sized and configured to be deflectedremotely within the renal artery by the caregiver. In this arrangement,less resistance to deflection is desirable. This is a function that thefirst flexure zone 32 need not perform. Accordingly, the deflectablesection 34 is desirably sized and configured to be less stiff (when thecontrol wire 40 is not actuated) and, importantly, to possess greaterflexibility than the first flexure zone 32 in at least one plane ofmotion.

Still, because the deflectable section 34, being distal to the firstflexure zone 32, precedes the first flexure zone 32 through the accessangle access angle α1, the deflectable section 34 also includesmechanical properties that accommodate its flexure or bending at thepreferred access angle α1, without fracture, collapse, substantialdistortion, or significant twisting of the elongated shaft 16.

The desired magnitude of axial stiffness, rotational stiffness, andflexibility for the deflectable section 34 can be obtained by selectionof constituent material or materials to provide a desired elasticmodulus (expressed, e.g., in terms of a Young's Modulus (E)) indicativeof flexibility, as well as by selecting the construct and configurationof the deflectable section 34, e.g., in terms of its interior diameter,outer diameter, wall thickness, and structural features, includingcross-sectional dimensions and geometry. Representative examples will bedescribed in greater detail later. Axial stiffness, torsional stiffness,and flexibility are properties that can be measured and characterized inconventional ways.

As before described, both the first flexure zone and deflectable section32 and 34 desirably include the mechanical properties of axial stiffnesssufficient to transmit to the energy delivery element 24 an axiallocating force. By pulling back on the handle assembly 200, axial forcesare transmitted by the force transmitting section 30 and the firstflexure zone and deflectable section 32 and 34 to retract the energydelivery element 24 in a proximal direction (away from the kidney)within the renal artery. Likewise, by pushing forward on the handleassembly 200, axial forces are transmitted by the force transmittingsection 30 and the first flexure zone and deflectable section 32 and 34to advance the energy delivery element 24 in a distal direction (towardthe kidney) within the renal artery. Thus, proximal retraction of thedistal end region 20 and energy delivery element 24 within the renalartery can be accomplished by the caregiver by manipulating the handleassembly 200 or shaft from outside the intravascular path 14.

As before described, both the first flexure zone and deflectable section32 and 34 also desirably include torsional strength properties that willallow the transmission of sufficient rotational torque to rotate thedistal end region 20 of the treatment device 12 such that the energydelivery element 24 is alongside the circumference of the blood vesselwall when the deflectable section 34 is deflected. By pulling or pushingon the actuator to deflect the energy delivery element 24 such that itachieves vessel wall contact, and then rotating the force transmittingsection 30 and, with it, the first flexure zone and deflectable section32 and 34, the energy delivery element 24 can be rotated in acircumferential path within the renal artery. As described later, thisrotating feature enables the clinical operator to maintain vessel wallcontact as the energy delivery element 24 is being relocated to anothertreatment site. By maintaining wall contact in between treatments, theclinical operator is able to achieve wall contact in subsequenttreatments with higher certainty in orientations with poorvisualization.

4. Force Redirecting Element

As shown in FIG. 7A the distal end region 20 comprises a distal assembly53 which comprises a force redirecting element 49, a force dampeningsection 44, and an energy delivery element 24. In some embodiments theforce redirecting element 49 is connected to the elongated shaft 16distal to the deflectable section 34; the force redirecting element 49is further joined to a force dampening section 44 which is joined to anenergy delivery element 24 positioned at the distal most point of theelongated shaft. In some embodiments the force redirecting element 49 ispart of the force dampening section 44. In other embodiments the forceredirecting element 49 is part of the deflectable section 34. It shouldbe understood that the force redirecting element can be usedinterchangeably with pre-shaped geometry.

In some embodiments it may be desirable to establish proximity to andalignment between the energy delivery element 24 and specific targetregions of tissue along an interior wall of the renal artery. Aspreviously discussed, renal arteries may vary in length, diameter andtortuosity. Establishing proximity to and alignment between the energydelivery element 24 and specific target regions may require advancingthe distal end region 20 through a renal artery with a high degree oftortuosity. As will be discussed in greater detail later, in someembodiments, the distal end region comprises a distal assembly 53comprising a force redirecting element 49 specially sized and configuredto facilitate advancement through renal arteries of various tortuosityand dimension while reducing the risk of exerting traumatic forces tothe interior wall of the renal artery. In some embodiments a forceredirecting element 49 is configured to facilitate contact between theenergy delivery element 24 and target regions of a wall of the renalartery. In some embodiments a force redirecting element 49 is configuredto facilitate the establishment and maintenance of stable contact forcebetween the energy delivery element 24 and a wall of the renal arteryprior to and during delivery of energy.

Advancement of a catheter through a renal artery can involve navigatingthe catheter through tight bends as shown in FIG. 8D. Considering thefragility of the renal artery wall, especially in patients with vasculardisease (e.g., arthrosclerosis), the risk of trauma during catheteradvancement is a concern. The force redirecting element 49, incombination with the deflectable section 34, force dampening section 44and energy delivery element 24, is specially shaped and configured toreduce the risk of traumatic contact force between the catheter andrenal artery wall as the catheter is advanced. Trauma can be caused byover distending, perforating and/or puncturing the renal artery walland/or scraping the wall and disrupting the epithelial tissue. A forceredirecting element 24 can reduce the risk of trauma by means of i)displacing an axial load on a catheter column to an eccentric loadand/or a side load to facilitate buckling of the catheter shaft, ii)changing the direction of a force applied to a renal artery wall, iii)reducing pressure exerted to the renal artery wall by increasing surfacearea, and/or iv) facilitating navigation around a sharp bend.

For purposes of discussing the force interactions between the catheterand artery wall a simplified example with an effectively stiff andstraight catheter 300 (as shown in FIG. 8A) follows. As discussed inmore detail later, variables such as catheter flexibility, dimensions,and geometry as represented by the present invention modify the forceinteractions. Every force has both a magnitude and direction. Themagnitude of the force applied by an effectively stiff and straightcatheter on to the artery wall is essentially equal to the force appliedby the caregiver advancing the catheter into the body. In this examplethe essentially straight and stiff catheter is advanced into a renalartery by pushing the proximal end of the catheter, thus the catheter'sadvancing trajectory is translation along the catheter's axis.Therefore, the direction of the force applied by the catheter on theartery wall is forward along the catheter's axis. In this simplifiedexample, the artery wall is represented by an elastic wall that has amaximum distension and wall strength. The force exerted by the arterywall includes a normal force, the component perpendicular to thesurface, which is characterized by the artery wall's ability towithstand distension and puncture (a function of elasticity andstrength); and the component parallel to the artery wall surface, whichis characterized by the friction between the artery wall and cathetersurface.

A straight catheter shaft is similar to a column which can withstand asignificant load along its axis before deforming. A load applied to theside of a column will cause it to bend at a lower force than an axialload. A load applied parallel to the column but at a distance from itsaxis, an eccentric load, will cause the column to buckle with a smallerload than an axial load. The more eccentric the load the smaller theforce required to buckle the column. A specially configured forceredirecting element 49 distances the distal tip of the catheter from theaxis such that as the distal tip is advanced into a renal artery wallthe load applied to all parts of the distal end region 20 is eccentric.In particular, the load applied to the force dampening section 44 is atan angle to the axis, thereby promoting deformation or buckling of theforce dampening section 44; the load applied to the deflectable sectionis eccentric causing it to buckle as shown in FIGS. 8C and 8D. Thus, thedistal end region 20 is configured to deform under a load that is lessthan a load that could apply a pressure to an artery wall causingexcessive trauma, thereby reducing the risk of trauma to the renalartery wall. Examples of distal end regions 20 comprising differentembodiments of force redirecting element 49 are shown in FIGS. 10A to10E.

FIGS. 9A to 9D provide a conceptual illustration of the force vectorsthat may exist as a catheter is advanced within the artery. For example,F_(C) corresponds to a force vector applied by a catheter, which isbroken out into a component vector parallel to the artery wall, F_(CP),and perpendicular or normal to the artery wall, F_(CN). Likewise, F_(A)corresponds to a force vector applied by the artery wall, which isbroken out into a component vector parallel to the artery wall, F_(AP),and perpendicular to the artery wall, F_(AN). F_(R) corresponds to aresultant force vector.

As illustrated in FIGS. 9A to 9D, when the catheter's trajectory isparallel to the artery wall the catheter may glide through the arteryoccasionally glancing off the wall contacting at the tip or along theside of the catheter's shaft. The force applied to the artery wall wouldbe parallel to the wall and there would be minimal normal componentF_(CN) with small parallel component F_(CP). As the angle of thecatheter's trajectory with the wall increases to a small acute angle thenormal and frictional reactive components increase. If the normal andfrictional components are not exceeded the vessel wall will stay intactand the catheter will slide against the wall. As the angle of thecatheter's trajectory with the wall increases to a larger acute angle,the normal component increases, increasing the risk of trauma byscraping or puncture. The following scenarios are illustrated with forcevectors in FIGS. 9A to 9D.

-   -   If F_(CP)<=F_(AP) and F_(CN)<=F_(AN), then F_(R)=0 and the        catheter will not move nor exert trauma to the artery wall.        (FIG. 9A)    -   If F_(CP)<=F_(AP) and F_(CN)>F_(AN), then F_(R) is of a        magnitude and direction that could cause the catheter to distend        or perforate the artery wall. (FIG. 9B)    -   If F_(CP)>F_(AP) and F_(CN)<=F_(AN), then F_(R) is of a        magnitude and direction that could cause the catheter to slide        forward with no trauma. (FIG. 9C)    -   If F_(CP)>F_(AP) and F_(CN)>F_(AN), then F_(R) is of a magnitude        and direction that could cause the catheter to slide forward and        distend the artery wall and possibly cause scraping trauma to        the epithelial layer. (FIG. 9D)

If a catheter's trajectory is essentially at a perpendicular angle withthe wall of the artery there is very little parallel component andmostly normal component. Any force applied to advance the catheter willbe directed straight into the artery wall creating a very high risk ofpuncture trauma. Angles that are close to perpendicular will have alarge normal component and some parallel component which can causescraping trauma. In some embodiments as described later, a speciallyconfigured force redirecting element 49 in combination with forcedampening section 44, deflectable section and first flexure zone 32 canmitigate this risk, first by promoting a portion of the catheter shaftto buckle under an eccentric load, then by changing a direction of theexerted force to redistribute the normal force component to moreparallel force component as shown in FIGS. 8C and 8D.

Furthermore, the pressure applied by the catheter to the artery wall isthe force divided by the area of contact. If only the tip of thecatheter contacts the artery wall, the pressure is equal to the forcedivided by the contacting surface area of the tip. If the cathetercontacts the artery wall over a large contacting surface area SA such asalong the side of an energy delivery element 24 and force dampeningsection 44, as shown in FIG. 8C, then the pressure is greatly reduced asthe force is divided by a much larger area. For example, the pressureexerted by a catheter with a 0.049″ diameter tip is about equal to theforce applied to an area of a 0.049″ circle which is about 530 times theforce. With a specially configured force redirecting element 49 acatheter can contact the artery wall over an area of about 0.0076 inchessquared applying a pressure of about 131 times the force. This featureprovides a force reduction of approximately 75% or more.

A specially configured force redirecting element 49 can also facilitatenavigation around a tight bend in a renal artery. As described in moredetail later, a force redirecting element 49 has dimensions and geometrythat allows the distal end of the catheter 57 to advance around a bendin a renal artery ahead of the catheter's axis and facilitates flexureof the force dampening section.

In some embodiments a force redirecting element is specially configuredto further facilitate placement of an energy delivery element 24 inalignment with an inner wall of a renal artery. A force redirectingelement 49 can facilitate placement of an energy delivery element 24 inalignment with an inner wall of a renal artery by means of i) providingmultiple direction deflection of a deflectable section 34 about the axiswith a force redirecting element 49 located on the deflectable section34, or ii) deflecting the distal end region in multiple directionstoward the renal artery wall when a force redirecting element 49 isspecially configured to be used with a delivery sheath.

In some embodiments a deflectable section 34 is configured forsingle-direction deflection and the placement of an energy deliveryelement 24 in contact with an inner wall of a renal artery in variousradial directions about the catheter axis is accomplished bycombinations of deflecting the deflectable section 34 and rotating thecatheter as will be discussed in more detail later. In some embodimentsa deflectable section 34 is configured for multiple direction deflectionwhich can facilitate the placement of an energy delivery element 24 incontact with an inner wall of a renal artery with less need for rotatingthe catheter. In some embodiments with single direction deflection, aforce redirecting element 49 can further facilitate placement of anenergy delivery element 24 by providing off axis displacement of theenergy delivery element 24 in additional radial directions about thecatheter axis. For example, in some embodiments a force redirectingelement 49 distances an energy delivery element 24 from the catheteraxis in an opposite direction than the biased deflection of adeflectable section 34. As shown in FIG. 11A a force redirecting element49 displaces an energy delivery element 24 above the undeflecteddeflectable section 34 and the energy delivery element 24 exerts astable contact force on, and is aligned with, the inner wall of a renalartery through flexure of a force dampening section 44. As shown in FIG.12A without rotating the catheter, the deflectable section 34 isdeflected to bring the energy delivery element 24 in alignment with, andexerting a stable contact force on, the inner wall of the renal artery.

In yet another embodiment shown in FIGS. 18A through 18G a forceredirecting element 49 is located in a deflectable section 34 anddistances the energy delivery element 24 a predetermined distance fromthe axis of the catheter in the opposite direction from the biaseddeflection of the deflectable section 34 when the deflectable section 34is not deflected. Partial deflection of the deflectable section 34straightens the deflectable section 34 and full deflection of thedeflectable section 34 deflects it in the biased deflection direction.This embodiment facilitates placement of an energy delivery element 24in multiple directions about the catheter axis without multiple controlwires and with less need for rotation.

In the embodiments shown in FIGS. 22A through 22F a distal assembly 53comprises two force redirecting elements 49′ and 49″ longitudinallyspaced apart. This embodiment utilizes force redirecting elements 49′and 49″ to facilitate placement of an energy delivery element 24 incontact with an inner wall of a renal artery at various locations usingmultiple direction deflection without the requirement of a deflectablesection 34. This embodiment is employed with a delivery sheath 95. Whenthe distal end region 20 is retracted within the delivery sheath 95 theforce redirecting elements 49′ and 49″ are flexibly conformed to thedelivery sheath 95. When the delivery sheath is pulled back to exposethe first force redirecting element 49′ the force dampening section 44is deflected in the direction of angle α8. When the delivery sheath 95is further pulled back to expose a second force redirecting element 49″the force dampening section 44 is deflected in a new direction that is acumulative effect of both angles α8 and α9. In this embodiment thedistal assembly 53 is configured so that the energy delivery element 24is sufficiently distanced from the axis of the catheter to be placed incontact with renal artery wall with stable contact force.

In a similar embodiment shown in FIG. 22G a force redirecting element 49comprises a helical bend such that as a delivery sheath 95 is pulledback gradually exposing the force redirecting element 49 the forcedampening section 44 is deflected in a rotating radial direction aboutthe axis placing an energy delivery element 24 at different locationscircumferentially spaced around the inner wall of the renal artery.

As shown in FIGS. 23A to 23D another embodiment comprises an energydelivery element 24 mounted distally to a force dampening section 44made of a long flexible element, such as a wire or tube, which isslidably engaged in a lumen 17 of an elongated tubular body 16 and aforce redirecting element 49. The force redirecting element 49 directsthe force dampening section 44 off-axis from the elongated tubular body16 so that the energy delivery element 24 is distanced from the axis ofthe elongated tubular body and the benefits of catheter navigation withreduced risk of trauma, as described earlier, are realized. Once distalend region 20 is navigated to a desired location in a renal artery, theforce dampening section 44 is telescopically advanced through the lumen17 by advancing the proximal end of the force dampening section 44 suchthat the energy delivery element 24 is placed at a greater distance fromthe axis of the elongated tubular body 16 until the energy deliveryelement 24 is placed in contact with an inner wall of a renal artery. InFIG. 23D the force dampening section 44 further comprises a distal forceredirecting element 49′ that distances the distal end of the energydelivery element 24 from the axis of the force dampening section 44 toredirect any force exerted to the energy delivery element 24 away froman axial load on the force dampening section 44 to promote buckling ofthe force dampening section 44 and reduce the risk of trauma that couldbe caused by telescopically advancing the force dampening section 44 andto facilitate alignment of the energy delivery element 24 in contactwith the inner wall of the renal artery. Placement and stable contactforce of the energy delivery element 24 is facilitated by the forceredirecting element 49, which redirects the force dampening section 44away from the axis of the elongated tubular structure.

5. Force Dampening Section

As FIGS. 7A, 7B, 7C, and 7D show, the distal end region 20 of theelongated shaft 16 also optionally may include, distal to the optionaldeflectable section 34, and distal to a force redirecting element 49, aforce dampening section 44. In this arrangement, the length L3 of thedeflectable section 34 may be shortened by a length L4, which comprisesthe length of the force dampening section 44. In this arrangement, theenergy delivery element 24 is carried at the end of the force dampeningsection 44. It should be understood that the term force dampeningsection can be used interchangeably with third flexure zone or distalflexure zone or passively flexible structure.

As FIG. 7D shows, the force dampening section 44 is sized, configured,and has the mechanical properties that accommodate additional flexure orbending, independent of the first flexure zone 32 and the deflectablesection 34, at a preferred treatment angle α3. The force dampeningsection 44 should also accommodate flexure sufficient for the distal endregion 20 to advance via a guide catheter into the renal artery withoutstraightening out the guide catheter or causing injury to the bloodvessel. The treatment angle α3 provides for significant flexure aboutthe axis of the distal end region 20 (a representative embodiment isshown in FIG. 16B). Not under the direct control of the physician,flexure at the force dampening section occurs in response to contactbetween the energy delivery element 24 and wall tissue occasioned by theradial deflection of the energy delivery element 24 at the deflectablesection 34 (see FIG. 6B). Passive deflection of the force dampeningsection provides the clinical operator with visual feedback viafluoroscopy or other angiographic guidance of vessel wall contact (asshown in FIGS. 27A to 27E). Additionally, the force dampening sectiondesirably orients the region of tissue contact along a side of theenergy delivery element 24, thereby increasing the area of contact. Theforce dampening section 44 also biases the energy delivery element 24against tissue, thereby stabilizing the energy delivery element 24.

The function of the force dampening section 44 provides additionalbenefits to the therapy. As actuation of the control wire 40 deflectsthe deflectable section 34, pressing the energy delivery element 24against an inner wall of an artery the force dampening sectioneffectively dampens the contact force between the energy deliveryelement 24 and the vessel wall. This effect is particularly valuable ina renal artery treatment due to movement of the renal artery caused byrespiration and/or pulsatile flow. While the flexibility of the firstflexure zone allows the distal end region of the treatment catheter tofollow movement of the renal artery during respiration, the increasedaxial stiffness of the deflected deflectable section provides helpfulintegrity to the distal end region to maintain contact between theenergy delivery element and vessel wall. The force dampening sectionhelps soften or cushion the contact force so that atraumatic contact canbe achieved and maintained, particularly during movement of the renalartery. By dampening this contact force, the force dampening sectionminimizes the chance of mechanical injury to the vessel wall and avoidsexcessive contact between the energy delivery element and vessel wall(see discussion of active surface area).

As FIG. 7A shows, the force dampening section 44 is desirably sized andconfigured in length L4 to be less than length L3. This is because, interms of length, the distance required for orienting and stabilizing theenergy delivery element 24 in contact with a wall of the renal artery issignificantly less than the distance required for radially deflectingthe energy delivery element 24 within the renal artery. In someembodiments, length L4 can be as long as about 1 cm. In otherembodiments, the length L4 is from about 2 mm to about 5 mm. In onerepresentative embodiment, the length L4 is about 5 mm. In anotherrepresentative embodiment, the length L4 is about 2 mm. In anotherrepresentative embodiment wherein the deflectable section 34 iscomprised of a hinge joint, the length L4 is about 16 mm which in thisembodiment can be greater than the length L3 of the deflectable section34.

When the catheter is outside the patient and the force dampening section44 is in a substantially straight, non-deflected configuration,treatment angle α3 (as shown in FIG. 7D) is approximately 180°. Uponfull deflection of the force dampening section 44, the angle α3 isreduced to anywhere between about 45° and 180°. In a representativeembodiment, upon full deflection, angle α3 is about 75° to about 135°.In another representative embodiment, upon full deflection, angle α3 isabout 90°.

In the passively deflected configuration of FIG. 7D, the force dampeningsection 44 comprises a radius of curvature RoC₃. In embodiments wherethe curvature of force dampening section 44 does not vary or isconsistent along the length L4, the length L4 and the contact angle α3may define the radius of curvature RoC₃. It should be understood thatthe curvature of force dampening section 44, and thereby the radius ofcurvature RoC₃ of the force dampening section, alternatively may varyalong the length L4.

In such embodiments where the curvature does not vary, the length L4 maydefine a fraction (180°−α3)/360° of the circumference C₃ of a circlewith an equivalent radius of curvature RoC₃. Thus, the circumference ofsuch an equivalent circle is:

$\begin{matrix}{C_{3} = {{\frac{360{^\circ}}{\left( {{180{^\circ}} - {\alpha \; 3}} \right)} \times L\; 4} = {2\pi \times {RoC}_{3}}}} & (14)\end{matrix}$

Solving for the radius of curvature RoC₂:

$\begin{matrix}{{RoC}_{3} = \frac{360{^\circ} \times L\; 4}{2\pi \times \left( {{180{^\circ}} - {\alpha \; 3}} \right)}} & (15)\end{matrix}$

Thus, in a representative embodiment of the force dampening section 44where the curvature of the force dampening section does not vary alongthe length L4, where the length L4 is about 2 mm to about 5 mm, andwhere the contact angle α3 is about 75° to about 135°, the radius ofcurvature RoC₃ is about 1 mm to about 6 mm.

As will be apparent, Equation (15) may be rearranged such that thelength L4 and the radius of curvature RoC₃ define the contact angle α3.Furthermore, Equation (15) may be rearranged such that the radius ofcurvature RoC₃ and the angle α3 define the length L4. Thus, inembodiments where the curvature of force dampening section 44 does notvary along the length L4, any one of the length L4, angle α3 and radiusof curvature RoC₃ may be specified by specifying the other twovariables.

The mechanical properties of force dampening section 44 and thedeflectable section 34 in terms of axial stiffness, torsional stiffness,and flexibility can be comparable. However, the force dampening section44 can be sized and configured to be less stiff and, importantly, topossess greater flexibility than the deflectable section 34.

In the embodiment just described (and as shown in FIG. 7D), the distalend region 20 may comprise a first flexure zone 32, a deflectablesection 34, and a force dampening section 44. The first flexure zone,deflection section, and force dampening section function independentlyfrom each other, so that the distal end region 20 of the elongated shaft16 can, in use, be placed into a more compound, complex, multi-bendstructure 36. The compound, complex, multi-bend structure 36 comprises afirst deflection region at the access angle α1 over a length L2 (thefirst flexure zone 32); an second deflection region at the contact angleα2 over a length L3 (the deflectable section 34); and a third deflectionregion at the treatment angle α3 over a length L4 (the force dampeningsection 44). In the compound, complex, multi-bend structure 36, alllengths L2, L3, and L4 and all angles α1, α2, and α3 can differ. This isbecause the angle α1 and length L2 are specially sized and configured togain access from an aorta into a respective renal artery through afemoral artery access point; the angle α2 and length L3 are speciallysized and configured to align an energy delivery element 24 element withan interior wall inside the renal artery; and the angle α3 and length L4are specially sized and configured to optimize surface contact betweentissue and the energy delivery element/heat transfer element.

The composite length of L2, L3 and L4 of the first flexure zone,deflectable section and force dampening section, respectively, of thedistal end region 20, along with the length L1 of the force transmittingsection 30 and the length L5 (see FIG. 11A) of the energy deliveryelement 24 (i.e., the composite length equal to L1+L2+L3+L4+L5),specifies a working length of the elongated shaft 16 of the treatmentdevice 12. In some representative embodiments, this working length isabout 40 cm to about 125 cm. In a representative embodiment where noguide catheter is used, then this working length may be about 40 cm toabout 50 cm. If, alternatively, a 55 cm length guide catheter is used,then this working length may be about 70 cm to about 80 cm. If a 90 cmlength guide catheter is used, then this working length may be about 105cm to about 115 cm.

C. Size and Configuration of the Energy Delivery Element for AchievingNeuromodulation in a Renal Artery

In some patients, it may be desirable to create multiple focal lesionsthat are circumferentially spaced along the longitudinal axis of therenal artery. However, it should be understood that a single focallesion with desired longitudinal and/or circumferential dimensions, oneor more full-circle lesions, multiple circumferentially spaced focallesions at a common longitudinal position, and/or multiplelongitudinally spaced focal lesions at a common circumferential positionalternatively or additionally may be created.

Creating multiple focal lesions that are circumferentially spaced alongthe longitudinal axis of the renal artery avoids the creation of afull-circle lesion, thereby reducing a risk of vessel stenosis, whilestill providing the opportunity to circumferentially treat the renalplexus, which is distributed about the renal artery. It is desirable foreach lesion to cover at least 10% of the vessel circumference toincrease the probability of affecting the renal plexus. However, it isimportant that each lesion not be too large (e.g., >60% of vesselcircumference) lest the risk of a stenotic effect increases (or otherundesirable healing responses such as thrombus formation or collateraldamage). In one embodiment the energy delivery element 24 is configuredto create a lesion at least 30% (i.e., greater than or equal to 30%) ofthe vessel circumference. In another embodiment, the energy deliveryelement 24 is configured to create a lesion of greater than or equal to30% but less than 60% of the vessel circumference. It is also importantthat each lesion be sufficiently deep to penetrate into and beyond theadventitia to thereby affect the renal plexus. However, lesions that aretoo deep (e.g., >5 mm) run the risk of interfering with non-targettissue and tissue structures (e.g., renal vein) so a controlled depth ofthermal treatment is desirable.

As described in greater detail below, energy delivery element 24 may bedelivered to a first treatment site within the renal artery such thatthe energy delivery element 24 is positioned in contact with an interiorwall of the artery for treating the renal plexus (see FIG. 24C). Oncepositioned within the artery as desired, energy may be delivered via theenergy delivery element to create a first focal lesion at this firsttreatment site (see FIG. 24D). The first focal lesion creates a firsttreatment zone 98 a that is not continuous completely around thecircumference of the renal artery in a radial plane or cross-sectionnormal to the wall or to the longitudinal axis of the artery (i.e., thefirst focal lesion does not extend all the way around the circumferenceof the vessel wall). As a result, there is a discrete untreated zoneabout the circumference of the artery in the radial plane of the firsttreatment zone normal to the longitudinal axis of the artery.

After formation of the first focal lesion at the first treatment zone 98a, the energy delivery element 24 optionally may be angularlyrepositioned relative to the renal artery (see FIGS. 24E and 24F). Thisangular repositioning may be achieved, for example, by angularlyrotating the elongated shaft 16 of treatment device 12 via handleassembly 200 (see FIG. 17A). In addition to angular repositioning of theenergy delivery element 24, the energy delivery element optionally maybe repositioned along the lengthwise or longitudinal dimension of therenal artery (see FIG. 24E). This longitudinal repositioning may beachieved, for example, by translating the elongated shaft 16 oftreatment device 12 via handle assembly 200, and may occur before, afteror concurrent with angular repositioning of the energy delivery element24.

Repositioning the energy delivery element 24 in both the longitudinaland angular dimensions places the energy delivery element in contactwith the interior wall of the renal artery at a second treatment sitefor treating the renal plexus (see FIG. 24E). Energy then may bedelivered via the energy delivery element to form a second focal lesionat this second treatment site, thereby creating a second treatment zone98 b and a second untreated zone (see FIG. 24F).

As with the first treatment zone created by the first focal lesion, thesecond treatment zone is not continuous about the complete circumferenceof the renal artery. However, the first and second treatment zones (aswell as the first and second untreated zones) are angularly andlongitudinally offset from one another about the angular and lengthwisedimensions of the renal artery, respectively (see FIG. 24G).Superimposing the first and second treatment zones, which are positionedalong different cross-sections or radial planes of the renal artery,about a common cross-section provides a composite treatment zone thatcovers a greater portion of the circumference of the artery than eithertreatment zone individually. As this composite treatment zone is notcontinuous (i.e., it is formed from multiple, longitudinally andangularly spaced treatment zones), it is expected that a greater portionof the circumference of the arterial wall may be treated with reducedrisk of vessel stenosis, as compared to formation of a single focallesion covering an equivalent portion of the arterial circumference at asingle treatment site (i.e., at a single lengthwise position or about asingle cross-section of the renal artery).

One or more additional focal lesions optionally may be formed at one ormore additional angularly and longitudinally spaced treatment sites tocreated additional angularly and longitudinally spaced treatment zones(see FIGS. 24E-24H). In one representative embodiment, superimpositionof all or a portion of the treatment zones provides a compositetreatment zone that is non-continuous (i.e., that is broken up along thelengthwise dimension or longitudinal axis of the renal artery), yet thatis substantially circumferential (i.e., that substantially extends allthe way around the circumference of the renal artery over a lengthwisesegment of the artery). This superimposed treatment zone beneficiallydoes not create a continuous circumferential lesion along any individualradial plane or cross-section normal to the artery, which may reduce arisk of acute or late stenosis formation, as compared to circumferentialtreatments that create such continuous circumferential lesions.

Non-continuous circumferential treatment by positioning energy deliveryelement(s) at different angular orientations along multiple lengthwiselocations may preferentially affect anatomical structures thatsubstantially propagate along the lengthwise dimension of the artery.Such anatomical structures can be neural fibers and/or structures thatsupport the neural fibers (e.g., the renal plexus). Furthermore, suchnon-continuous circumferential treatment may mitigate or reducepotentially undesirable effects induced in structures that propagateabout the angular dimension of the artery, such as smooth muscle cells.Were a continuous circumferential lesion alternatively to be formed, theangular or circumferential orientation of the smooth muscle cellsrelative to the artery may increase a risk of acute or late stenosis oracute vessel spasm.

In multi-energy delivery element configurations (e.g., multi-electrodeconfigurations), such as in FIG. 6C, multiple non-continuouscircumferential treatment zones can be created during a single catheterplacement within the renal artery. The multiple energy delivery elementscan be spaced and located such that they are longitudinally andangularly spaced apart from one another and such that they createlongitudinally offset and angularly opposed or offset treatment zones.Retraction and rotation of the treatment device 12 can reposition theenergy delivery elements to create additional longitudinally andangularly separated treatment zones, thereby allowing the practitionerthe ability to create multiple treatment zones per catheter placementand several treatment zones via only two catheter placements.

As described (and as FIG. 11A shows), the energy delivery element 24 issized and configured, in use, to contact an internal wall of the renalartery. In the illustrated embodiment (see FIG. 11B), the energydelivery element 24 takes the form of an electrode 46 sized andconfigured to apply an electrical field comprising radiofrequency (RF)energy from the generator 26 to a vessel wall. In the illustratedembodiment, the electrode 46 is operated in a monopolar or unipolarmode. In this arrangement, a return path for the applied RF electricfield is established, e.g., by an external dispersive electrode (shownas 38 in FIG. 6A), also called an indifferent electrode or neutralelectrode. The monopolar application of RF electric field energy servesto ohmically or resistively heat tissue in the vicinity of the electrode46. The application of the RF electrical field thermally injures tissue.The treatment objective is to thermally induce neuromodulation (e.g.,necrosis, thermal alteration or ablation) in the targeted neural fibers.The thermal injury forms a lesion in the vessel wall, which is shown,e.g., in FIG. 12B. Alternatively, a RF electrical field can be deliveredwith an oscillating intensity that does not thermally injure the tissuewhereby neuromodulation in the targeted nerves is accomplished byelectrical modification of the nerve signals.

The active surface area of contact (ASA) between the energy deliveryelement 24 or electrode 46 and the vessel wall has great bearing on theefficiency and control of the transfer of a thermal energy field acrossthe vessel wall to thermally affect targeted neural fibers in the renalplexus (RP). The active surface area of the energy delivery element 24and electrode 46 is defined as the energy transmitting area of theelement 24 or electrode 46 that can be placed in intimate contactagainst tissue. Too much contact between the energy delivery element andthe vessel wall and/or too much power may create unduly hightemperatures at or around the interface between the tissue and theenergy delivery element, thereby creating excessive heat generation atthis interface and/or spasm and contraction of the vessel wall. Thisexcessive heat can also create a lesion that is circumferentially toolarge, increasing the risk of stenosis. This excessive heat can alsolead to undesirable thermal damage at the vessel wall, which stiffensand desiccates the vessel tissue making it more susceptible to punctureand perforation. Additionally, the tissue desiccation (i.e.,dehydration) reduces the electrical and thermal conductivity of thetissue. Reduced conductivity may potentially create a lesion that is tooshallow to reach the neural fibers and may also result in the buildup ofexcessive heat, causing increased and undesirable damage to the vesselwall and increasing the likelihood of thrombus formation. Although therisks of excessive wall contact and heating are many, too little contactbetween the energy delivery element and the vessel wall may impair theefficacy of the treatment. For example, too little contact may result insuperficial heating of the vessel wall, thereby creating a lesion thatis too small (e.g., <10% of vessel circumference) and/or too shallow toreach the target renal neural fibers.

While the active surface area (ASA) of the energy delivery element 24and electrode 46 is important to creating lesions of desirable size anddepth, the ratio between the active surface area (ASA) and total surfacearea (TSA) of the energy delivery element 24 and electrode 46 is alsoimportant. The ASA to TSA ratio influences lesion formation in two ways:(1) the degree of resistive heating via the electric field, and (2) theeffects of blood flow or other convective cooling elements such asinjected or infused saline. As discussed above, the RF electric fieldcauses lesion formation via resistive heating of tissue exposed to theelectric field. The higher the ASA to TSA ratio (i.e., the greater thecontact between the electrode and tissue), the greater the resistiveheating. As discussed in greater detail below, the flow of blood overthe exposed portion of the electrode (TSA-ASA) provides conductive andconvective cooling of the electrode, thereby carrying excess thermalenergy away from the interface between the vessel wall and electrode. Ifthe ratio of ASA to TSA is too high (e.g., 50%), resistive heating ofthe tissue can be too aggressive and not enough excess thermal energy isbeing carried away, resulting in excessive heat generation and increasedpotential for stenotic injury, thrombus formation and undesirable lesionsize. If the ratio of ASA to TSA is too low (e.g., 10%), then there istoo little resistive heating of tissue, thereby resulting in superficialheating and smaller and shallower lesions.

Various size constraints for the energy delivery element 24 may beimposed for clinical reasons by the maximum desired dimensions of theguide catheter, as well as by the size and anatomy of the renal arteryitself. Typically, the maximum outer diameter (or cross-sectionaldimension for non-circular cross-section) of the electrode 46 comprisesthe largest diameter encountered along the length of the elongated shaft16 distal to the handle assembly 200. Thus, the outer diameters of theforce transmitting section 30, first flexure zone 32, deflection section34 and force dampening section 44 are equal to or (desirably) less thanthe maximum outer diameter of the electrode 46.

In a representative embodiment shown in FIG. 11A, the electrode 46 takesthe form of a right circular cylinder, possessing a length L5 that isgreater than its diameter. The electrode 46 further desirably includes adistal region that is rounded to form an atraumatic end surface 48. Inthe representative embodiment shown in FIG. 11B, the electrode 46 isspherical in shape, such that the length L5 is equal to the electrode'sdiameter. The spherical shape, too, presents an atraumatic surface tothe tissue interface.

As shown in FIG. 8A, the angle α3 and length L4 of the distal assembly53 are specially sized and configured, given the TSA of the respectiveelectrode, to optimize an active surface area of contact between tissueand the respective electrode 46 (ASA). The angle α3 and the length L4 ofthe distal assembly 53 make it possible to desirably lay at least a sidequadrant 50 of the electrode 46 against tissue (see FIG. 12A), though itshould be understood that the electrode 46 does not necessarily need tobe positioned with its side quadrant 50 against tissue prior to powerdelivery. In a representative embodiment, the active surface area of theelectrode 46 contacting tissue (ASA) can be expressed as ASA≧0.25 TSAand ASA≦0.50 TSA.

An ASA to TSA ratio of over 50% may be effective with a reduced powerdelivery profile. Alternatively, increasing the convective cooling ofthe electrode that is exposed to blood flow can compensate for a higherASA to TSA ratio. As discussed further below, this could be achieved byinjecting or infusing cooling fluids such as saline (e.g., roomtemperature saline or chilled saline) over the electrode and into theblood stream.

The stiffnesses of each of the deflectable section 34 and forcedampening section 44 are also selected to apply via the electrode astabilizing force that positions the electrode 46 in substantiallysecure contact with the vessel wall tissue. This stabilizing force alsoinfluences the amount of wall contact achieved by the energy deliveryelement (i.e., the ASA to TSA ratio). With greater stabilizing force,the energy delivery element has more wall contact and with lessstabilizing force, less wall contact is achieved. Additional advantagesof the stabilizing force include, (1) softening the contact forcebetween the distal end 20 and vessel wall to minimize risk of mechanicalinjury to vessel wall, (2) consistent positioning of the electrode 46flat against the vessel wall, and (3) stabilizing the electrode 46against the vessel wall. As discussed above with respect to the combinedeffect of the first flexure zone and second/deflectable section, thisstabilizing force allows the catheter treatment device to maintainconsistent contact with the vessel wall even during motion of the renalartery during respiration. The stabilizing force also allows theelectrode to return to a neutral position after the electrode is removedfrom contact with the wall.

As previously discussed, for clinical reasons, the maximum outerdiameter (or cross-sectional dimension) of the electrode 46 isconstrained by the maximum inner diameter of the guide catheter throughwhich the elongated shaft 16 is to be passed through the intravascularpath 14. Assuming that an 8 French guide catheter 94 (which has an innerdiameter of approximately 0.091 inches) is, from a clinical perspective,the largest desired catheter to be used to access the renal artery, andallowing for a reasonable clearance tolerance between the electrode 46and the guide catheter, the maximum diameter of the electrode 46 isconstrained to about 0.085 inches. In the event a 6 French guidecatheter is used instead of an 8 French guide catheter, then the maximumdiameter of the electrode 46 is constrained to about 0.070 inches. Inthe event a 5 French guide catheter is used, then maximum diameter ofthe electrode 46 is constrained to about 0.053 inches. Based upon theseconstraints and the aforementioned power delivery considerations, theelectrode 46 desirably has a maximum outer diameter of from about 0.049to about 0.051 inches. The electrode 46 also desirably has a minimumouter diameter of about 0.020 inches to provide sufficient cooling andlesion size. In some embodiments, the electrode 46 (i.e., the energydelivery element 24) may have a length of about 1 mm to about 3 mm. Insome embodiments in which the energy delivery element is a resistiveheating element, it can have a maximum outer diameter from about 0.049to 0.051 inches and a length of about 10 mm to 30 mm.

D. Applying Energy to Tissue Via the Energy Delivery Element

Referring back to FIG. 5, in the illustrated embodiment, the generator26 may supply to the electrode 46 a pulsed or continuous RF electricfield. Although a continuous delivery of RF energy is desirable, theapplication of thermal energy in pulses may allow the application ofrelatively higher energy levels (e.g., higher power), longer or shortertotal duration times, and/or better controlled intravascular renalneuromodulation therapy. Pulsed energy may also allow for the use of asmaller electrode.

The thermal therapy may be monitored and controlled, for example, viadata collected with one or more sensors 52, such as temperature sensors(e.g., thermocouples, thermistors, etc.), impedance sensors, pressuresensors, optical sensors, flow sensors, chemical sensors, etc. (seeFIGS. 12A and 12B). Sensor(s) 52 may be incorporated into or onelectrode 46 and/or in/on adjacent areas on the distal end region 20and/or distal assembly 53.

Advantageously, since the deflectable section 34 deflects in acontrolled manner, the surface of electrode 46 that contacts tissueduring treatment may be known. As such, sensor(s) 52 may be incorporatedinto the electrode in a manner that specifies whether the sensor(s) arein contact with tissue at the treatment site and/or are facing bloodflow. The ability to specify sensor placement relative to tissue andblood flow is highly significant, since a temperature gradient acrossthe electrode from the side facing blood flow to the side in contactwith the vessel wall may be up to about 15° C. Significant gradientsacross the electrode in other sensed data (e.g., flow, pressure,impedance, etc.) also are expected.

The sensor(s) 52 may, for example, be incorporated on the side of theelectrode that contacts the vessel wall at the treatment site duringpower and energy delivery (see FIG. 12B), may be incorporated into thetip of the electrode, may be incorporated on the opposing side of theelectrode that faces blood flow during energy delivery (see FIG. 12A),and/or may be incorporated within certain regions of the electrode(e.g., distal, proximal, quandrants, etc.). In some embodiments,multiple sensors may be provided at multiple positions along theelectrode and/or relative to blood flow. For example, a plurality ofcircumferentially and/or longitudinally spaced sensors may be provided.In one embodiment, a first sensor may contact the vessel wall duringtreatment, and a second sensor may face blood flow.

Additionally or alternatively, various microsensors can be used toacquire data corresponding to the energy delivery element, the vesselwall and/or the blood flowing across the energy delivery element. Forexample, arrays of micro thermocouples and/or impedance sensors can beimplemented to acquire data along the energy delivery element or otherparts of the treatment device. Sensor data can be acquired or monitoredprior to, simultaneous with, or after the delivery of energy or inbetween pulses of energy, when applicable. The monitored data may beused in a feedback loop to better control therapy, e.g., to determinewhether to continue or stop treatment, and it may facilitate controlleddelivery of an increased or reduced power or a longer or shorterduration therapy.

Non-target tissue may be protected by blood flow (F) within therespective renal artery that serves as a conductive and/or convectiveheat sink that carries away excess thermal energy. For example (as FIGS.12A and 12B show), since blood flow (F) is not blocked by the elongatedshaft 16 and the electrode 46 it carries, the native circulation ofblood in the respective renal artery serves to remove excess thermalenergy from the non-target tissue and the energy delivery element. Theremoval of excess thermal energy by blood flow also allows fortreatments of higher power, where more power can be delivered to thetarget tissue as thermal energy is carried away from the electrode andnon-target tissue. In this way, intravascularly-delivered thermal energyheats target neural fibers located proximate to the vessel wall tomodulate the target neural fibers, while blood flow (F) within therespective renal artery protects non-target tissue of the vessel wallfrom excessive or undesirable thermal injury. When energy is deliveredin pulses, the time interval between delivery of thermal energy pulsesmay facilitate additional convective or other cooling of the non-targettissue of the vessel wall compared to applying an equivalent magnitudeor duration of continuous thermal energy.

It may also be desirable to provide enhanced cooling by inducingadditional native blood flow across the energy delivery element. Forexample, techniques and/or technologies can be implemented by thecaregiver to increase perfusion through the renal artery or to theenergy delivery element itself. These techniques include positioningpartial occlusion elements (e.g., balloons) within upstream vascularbodies such as the aorta or proximal portion of the renal artery toimprove flow across the energy delivery element.

In addition, or as an alternative, to passively utilizing blood flow (F)as a heat sink, active cooling may be provided to remove excess thermalenergy and protect non-target tissues. For example, a thermal fluidinfusate may be injected, infused, or otherwise delivered into thevessel in an open circuit system. Additionally or alternatively, theenergy delivery element 24 (e.g., electrode 46) may be actively cooledin a closed circuit system (i.e., without delivering any agents into thebloodstream) to remove excess thermal energy, such as by circulating athermal fluid infusate (e.g., a cryogenic or chilled fluid) within thedistal end region 20 or by some other mechanism.

Thermal fluid infusates used for active cooling may, for example,comprise (room temperature or chilled) saline or some otherbiocompatible fluid. The thermal fluid infusate(s) may, for example, beintroduced through the treatment device 12 via one or more infusionlumens and/or ports. When introduced into the bloodstream, the thermalfluid infusate(s) may, for example, be introduced through a guidecatheter at a location upstream from the energy delivery element 24 orelectrode 46, or at other locations relative to the tissue for whichprotection is sought. The delivery of a thermal fluid infusate in thevicinity of the treatment site (via an open circuit system and/or via aclosed circuit system) may, for example, allow for the application ofincreased/higher power, may allow for the maintenance of lowertemperature at the vessel wall during energy delivery, may facilitatethe creation of deeper or larger lesions, may facilitate a reduction intreatment time, may allow for the use of a smaller electrode size, or acombination thereof.

Although many of the embodiments described herein pertain to electricalsystems configured for the delivery of RF energy, it is contemplatedthat the desired treatment can be accomplished by other means, e.g., bycoherent or incoherent light; direct thermal modification (e.g., with aheated or cooled fluid or resistive heating element); microwave;ultrasound (including high intensity focused ultrasound); diode laser;radiation; a tissue heating fluid; and/or a cryogenic fluid.

III. REPRESENTATIVE EMBODIMENTS A. First Representative Embodiment(First Flexure Zone, Deflectable Section, Force Redirecting Element,Force Dampening Section, and Energy Delivery Element)

FIGS. 10A to 17B show a representative embodiment of an elongated shaft16 that includes a force transmitting section 30, as well as firstflexure zone 32, deflectable section 34, and distal assembly 53, havingthe physical and mechanical features described above. In thisembodiment, the distal assembly 53 comprises a force redirecting element49, a force dampening section 44, and an energy delivery element 24,wherein the force redirecting element 49 is part of the force dampeningsection 44 and is located near the proximal end of the force dampeningsection 44 (see, e.g., FIG. 14A).

1. Force Transmitting Section

In the illustrated embodiment, as shown in FIGS. 13A and 13B, the forcetransmitting section 30 comprises a first elongated and desirablytubular structure, which can take the form of, e.g., a first tubularstructure 54. The first tubular structure 54 is desirably a hypo tubethat is made of a metal material, e.g. of stainless steel, or a shapememory alloy, e.g., nickel titanium (a.k.a., Nitinol or NiTi), topossess the requisite axial stiffness and torsional stiffness, asalready described, for the force transmitting section 30. As alreadydescribed, the force transmitting section 30 comprises the most stiffsection along the elongated shaft 16, to facilitate axially movement ofthe elongated shaft 16, as well as rotational manipulation of theelongated shaft 16 within the intravascular path 14. Alternatively, thefirst tubular structure 54 may comprise a hollow coil, hollow cable,solid cable (w/ embedded wires), a braided or braid reinforced shaft, acoil reinforced polymer shaft, a metal/polymer composite, etc.

The stiffness is a function of material selection as well as structuralfeatures such as interior diameter, outside diameter, wall thickness,geometry and other features that are made by micro-engineering,machining, cutting and/or skiving the hypo tube material to provide thedesired axial and torsional stiffness characteristics. For example, theelongated shaft can be a hypo tube that is laser cut to various shapesand cross-sectional geometries to achieve the desired functionalproperties.

When the first tubular structure 54 is made from an electricallyconductive metal material, the first tubular structure 54 may include asheath 56 or covering made from an electrically insulating polymermaterial or materials, which is placed over the outer diameter of theunderlying tubular structure. The polymer material can also be selectedto possess a desired durometer (expressing a degree of stiffness or lackthereof) to contribute to the desired overall stiffness of the firsttubular structure 54. Candidate materials for the polymer materialinclude, but are not limited to, polyethylene terephthalate (PET);Pebax® material; nylon; polyurethane, Grilamid® material or combinationsthereof. The polymer material can be laminated, dip-coated,spray-coated, or otherwise deposited/attached to the outer diameter ofthe tube.

2. First Flexure Zone

As FIGS. 14A, 14B, and 14C show, the first flexure zone 32 comprises asecond elongated and desirably tubular structure, which can take theform of, e.g., a second tubular structure 58. The second tubularstructure 58 can be made from the same or different material as thefirst tubular structure 54. The axial stiffness and torsional stiffnessof the second tubular structure 58 possesses the requisite axialstiffness and torsional stiffness, as already described, for the firstflexure zone 32. As already described, the first flexure zone 32 may beless stiff and more flexible than the force transmitting section 30, tonavigate the severe bend at and prior to the junction of the aorta andrespective renal artery. The second tubular structure is desirably ahypo tube, but can alternatively comprise a hollow coil, hollow cable,braided shaft, etc.

It may be desirable for the first and second tubular structures 54 and58 to share the same material. In this event, the form and physicalfeatures of the second tubular structure 58 may be altered, compared tothe first tubular structure 54, to achieve the desired stiffness andflexibility differences. For example, the interior diameter, outsidediameter, wall thickness, and other engineered features of the secondtubular structure 58 can be tailored to provide the desired axial andtorsional stiffness and flexibility characteristics. For example, thesecond tubular structure 58 can be laser cut along its length to providea bendable, spring-like structure. Depending on the ease ofmanufacturability the first and second tubular structures may beproduced from the same piece of material or from two separate pieces. Inthe event the first tubular structure and second tubular structure arenot of the same material, the outside diameter of the second tubularstructure 58 can be less than the outer diameter of first tubularstructure 54 (or have a smaller wall thickness) to create the desireddifferentiation in stiffness between the first and second tubularstructures 54 and 58.

When the second tubular structure 58 is made from an electricallyconductive metal material, the second tubular structure 58, like thefirst tubular structure 54, includes a sheath 60 (see FIGS. 14B and 14C)or covering made from an electrically insulating polymer material ormaterials, as already described. The sheath 60 or covering can also beselected to possess a desired durometer to contribute to the desireddifferentiation in stiffness and flexibility between the first andsecond tubular structures 58.

The second tubular structure 58 can comprise a different material thanthe first tubular structure 54 to impart the desired differentiation instiffness and flexibility between the first and second tubularstructures 58. For example, the second tubular structure 58 can comprisea cobalt-chromium-nickel alloy, instead of stainless steel.Alternatively, the second tubular structure 58 can comprise a less rigidpolymer, a braided or braid-reinforced shaft, a coil reinforced polymershaft, a metal/polymer composite, nitinol or hollow cable-likestructure. In addition to material selection, the desireddifferentiation in stiffness and overall flexibility can be achieved byselection of the interior diameter, outside diameter, wall thickness,and other engineered features of the second tubular structure 58, asalready described. Further, a sheath 60 or covering made from anelectrically insulating polymer material, as above described, can alsobe placed over the outer diameter of the second tubular structure 58 toimpart the desired differentiation between the first and second tubularstructures 54 and 58.

3. Deflectable Section

As FIGS. 15A, 15B, 15C, and 15D show, the deflectable section 34comprises a third elongated and desirably tubular structure, which cantake the form of, e.g., a third tubular structure 62. The third tubularstructure 62 can be made from the same or different material as thefirst and/or second tubular structures 54 and 58. The axial stiffnessand torsional stiffness of the third tubular structure 62 possesses therequisite axial stiffness and torsional stiffness, as already described,for the deflectable section 34. As already described, the deflectablesection 34 may be less stiff and more flexible than the first flexurezone 32, to facilitate controlled deflection of the deflectable section34 within the respective renal artery.

If the second and third tubular structures 58 and 62 share the samematerial, the form and physical features of the third tubular structure62 are altered, compared to the second tubular structure 58, to achievethe desired stiffness and flexibility differences. For example, theinterior diameter, outside diameter, wall thickness, and otherengineered features of the third tubular structure 62 can be tailored toprovide the desired axial and torsional stiffness and flexibilitycharacteristics. For example, the third tubular structure 62 can belaser cut along its length to provide a more bendable, more spring-likestructure than the second tubular structure 58.

When the third tubular structure 62 is made from an electricallyconductive metal material, the third tubular structure 62 also mayinclude a sheath 64 (see FIGS. 15B, 15C, and 15D) or covering made froman electrically insulating polymer material or materials, as alreadydescribed. The sheath 64 or covering can also be selected to possess adesired durometer to contribute to the desired differentiation instiffness and flexibility between the second and third tubular structure62.

The third tubular structure 62 can comprise a different material thanthe second tubular structure to impart the desired differentiation instiffness and flexibility between the second and third tubularstructures 62. For example, the third tubular structure 62 can include aNitinol material, to impart the desired differentiation in stiffnessbetween the second and third tubular structures 58 and 62. In additionto material selection, the desired differentiation in stiffness andoverall flexibility can be achieved by selection of the interiordiameter, outside diameter, wall thickness, and other engineeredfeatures of the third tubular structure 62, as already described.

For example, in diameter, the outside diameter of the third tubularstructure 62 is desirably less than the outer diameter of second tubularstructure 58. Reduction of outside diameter or wall thickness influencesthe desired differentiation in stiffness between the second and thirdtubular structures 58 and 62.

As discussed in greater detail above, preferential deflection of thedeflectable section is desirable. This can be achieved by making thethird tubular structure 62 compressible in the desired direction ofdeflection and resilient to compression opposite the direction ofdeflection. For example, as shown in FIGS. 15B and 15C, the thirdtubular structure 62 (unlike the second tubular structure 58) caninclude a laser-cut pattern that includes a spine 66 with connectingribs 68. The pattern biases the deflection of the third tubularstructure 62, in response to pulling on the control wire 40 coupled tothe distal end of the third tubular structure 62, toward a desireddirection. The control wire 40 is attached to a distal end of thedeflectable section with solder 130. When the control wire is pulled thethird tubular structure compresses on the compressible side biasingdeflection in the direction of the compressible side. The benefits ofpreferential deflection within a renal artery have already beendescribed.

As also shown in FIG. 15D, a flat ribbon material 70 (e.g., Nitinol,stainless steel, or spring stainless steel) can be attached to the thirdtubular structure 62. When the pulling force is removed from the controlwire 40, the flat ribbon, which serves to reinforce the deflectablethird tubular structure 62, will elastically straighten out thedeflectable third tubular structure 62.

Further, a sheath 64 (see FIGS. 15B, 15C, and 15D) or covering made froman electrically insulating polymer material, as above described, andhaving a desired durometer can also be placed over the outer diameter ofthe second tubular structure 58 to impart the desired differentiationbetween the first and second tubular structures 54 and 58.

In the embodiment of FIGS. 15B-15D, the width of the spine 66 (i.e., theradial arc length of the spine 66 at regions along the longitudinal axisof the third tubular structure 62 that do not include ribs 68) affectsthe relative stiffness and elasticity of the third tubular structure 62.It should be understood that the width of the spine 66 may be specifiedto provide the third tubular structure 62 with a desired relativestiffness and/or elasticity. Furthermore, the width of the spine 66 mayvary along the longitudinal axis of the third tubular structure 62,thereby providing the third tubular structure with a varying relativestiffness and/or elasticity along its length. Such variation in thewidth of the spine 66 may be gradual, continuous, abrupt, discontinuous,or combinations thereof.

The length L3 of the deflectable section 34 is between about 5 mm and 20mm, for example less than or equal to about 12.5 mm. As the distal endregion 20 is advanced from a guide catheter into a renal artery theenergy delivery element 24 contacts the superior surface of the renalartery wall. The length L3 allows the energy delivery element 24 to bemanipulated through deflection of the deflectable section 34 to contactdorsal, ventral and inferior surfaces of the renal artery wall within ashort distance as long as a portion of the deflectable section 34protrudes from the guide catheter. Thus the length L3 of the deflectablesection 34 is chosen to be specially suited for use in a renal artery.

The width of the ribs 68 (i.e., the distance spanned by each rib alongthe longitudinal axis of the third tubular structure 62), as well as thespacing of the ribs 68 (i.e., the distance spanned by the spine 66 alongthe longitudinal axis of the third tubular member 62 between adjacentribs 68), optionally may affect a maximal preferential deflectionachievable by the deflectable section 34 before adjacent ribs 68 contactone another, i.e. may limit the maximum amount of compression to theside of the third tubular structure that is compressible. Such contactbetween adjacent ribs 68 optionally may define the radius of curvatureand/or the angle α2 (see FIG. 7C) of the deflectable section 34 undersuch maximal preferential deflection. The deflectable section isconfigured for a state of maximum flexure, wherein the state of maximumflexure is achieved when the deflectable body moves the energy deliveryelement away from the axis of the elongated tubular body by apredetermined distance. The maximum flexure avoids the risk of causingtrauma to the renal artery wall which could happen if a deflectablesection 34 of length L3 were deflected significantly more than thediameter of a renal artery. As will be discussed in more detail later,the force dampening section 44 is configured to dampen force exerted tothe artery wall when the deflectable section 34 is deflected. Stablecontact force between an energy delivery element 24 and an inner wall ofa renal artery can be created by exerting a force that is greater thanan instable force and less than a traumatic force. The force dampeningsection 44 dampens the contact force keeping it within a stable yetatraumatic range even when the deflectable section 34 moves the energydelivery element 24 away from the axis of the elongated tubular body bya distance greater than the diameter of a renal artery. For example, theforce dampening section 44 may flex enough for the deflectable section34 to be configured for a state of maximum flexure such that thepredetermined distance is about 4 mm greater than a renal arterydiameter. In one embodiment the distal assembly 53 has a length of about3 mm to 6 mm (e.g. less than or equal to 5 mm), the deflectable section34 has a length L3 of about 8 mm to 15 mm (e.g. less than or equal to12.5 mm) and has a maximum flexure displacing the energy deliveryelement 24 a predetermined distance of about 10 to 14 mm. Alternativelyor additionally, the predetermined distance can be adjusted by adeflection limiter in the handle 200 that limits the actuator 260 todisplacing the control wire a maximum amount thus limiting thedeflection to an adjusted state of maximum flexure.

It should be understood that the width and/or the spacing of the ribs 68may be specified as desired to achieve a desired maximal preferentialdeflection. Furthermore, the width and/or the spacing of the ribs 68 mayvary along the longitudinal axis of the third tubular structure 62,thereby providing the deflectable section 34 with a varying radius ofcurvature under such maximal preferential deflection. Such variation inthe width and/or spacing of the ribs 68 may be gradual, continuous,abrupt, discontinuous, or combinations thereof.

4. Force Redirecting Element

As shown in FIG. 16A the distal end region 20 comprises a distalassembly 53. Distal assembly 53 comprises a force redirecting element49, a force dampening section 44 and an energy delivery element 24,wherein the force redirecting element 49 is part of the force dampeningsection 44 and is located near the proximal end of the force dampeningsection 44. The force redirecting element 49 comprises a bend in theforce dampening section 44 adapted to induce buckling of at least one ofthe force dampening section 44, deflectable section 34, and a portion ofthe first flexure zone 32 at a force that is smaller than the maximumforce a renal artery wall can withstand before trauma is caused suchthat the risk of trauma is greatly reduced while advancing the distalend region 20 through a tortuous renal artery. Buckling is facilitatedby a) redirecting an axial load to an eccentric load along at least aportion of one of the deflectable section 34 and first flexure zone 32by distancing the distal end of the energy delivery element 24 from theaxis of an effective portion of the deflectable section 34 (and possiblyan effective portion of the first flexure zone 32) by a preset angle anddistance; or b) by redirecting an axial load to a side load along atleast a portion of the force dampening section 44 or deflectable section34. In this context the effective portion of the deflectable section 34and first flexure zone 32 refers to the portion that is in the renalartery and is not substantially constrained by a guide catheter or bybends in the renal artery.

In some embodiments force redirecting element 49 and force dampeningsection 44 comprise the same structure wherein the force redirectingelement is a preformed bend or curve in the force dampening section 44as shown in FIGS. 10A and 100. Alternatively, force redirecting elementcan be two preformed bends or curves in the force dampening section 44as shown in FIGS. 10B and 10D, or force redirecting element can be anynumber and combination of bends or curves that distance the distal tip57 of an energy delivery element 24 from the axis of the elongated body16 as shown in FIG. 10E.

In other embodiments force redirecting element 49 and force dampeningsection 44 can comprise separate structures. For example, as shown inFIG. 16H force redirecting element 49 is a wire or tube with a preformedangular bend. The force redirecting element can be connected to aseparate force dampening section 44, which in FIG. 16H is a spring coil.

Referring to FIG. 10A, a force redirecting element 49 can comprise anangular bend with an angle α4 between about 135° and 170°, for exampleless than or equal to about 160° and a radius of curvature RoC₄ betweenabout 0 mm and 1 mm, for example less than or equal to about 0.25 mm.The force redirecting element 49 can be positioned along the forcedampening section 44 within about 0 mm to 2 mm from the proximal end ofthe force dampening section 44, for example less than or equal to about0.25 mm. The length of the distal assembly 53 distal to the forceredirecting element 49 can be between 3 mm and 10 mm, for example lessthan or equal to about 5 mm.

Referring to FIG. 10B a force redirecting element 49 can comprise afirst angular bend with and angle α5 and radius of curvature RoC₅ and asecond angular bend with and angle α6 and radius of curvature RoC₆;wherein the angles α5 and α6 is between 135° and 170°, for example lessthan or equal to about 145°, radius of curvature RoC₅ and RoC₆ isbetween 0 mm and 2 mm, for example less than or equal to about 0.25 mm.

As shown in FIGS. 10C and 10D the force redirecting element 49 of thefirst representative embodiment can comprise one or two curves. Theforce redirecting element 49 can be a curved force dampening section 44.

As shown in FIG. 10D a force redirecting element 49 can comprise anypre-formed geometry that places the distal end of a catheter relative tothe axis of the deflectable section 34 by a preset angle α7 and distanceL7, wherein the preset angle α7 is between about 15° to 45°, for exampleless than or equal to about 20°, and the distance L7 is between about 1mm and 6 mm, for example less than or equal to about 2 mm.

The force redirecting elements described above can be oriented such thatthe energy delivery element 24 is displaced in a direction that is inabout the opposite direction and same plane as the predetermined biasedflexure of the deflectable section 34. Alternatively a force redirectingelement can be oriented such that the energy delivery element 24 isdisplaced in a direction that is in about the same direction and planeas the predetermined biased flexure of the deflectable section 34.

As shown in FIG. 16B the force redirecting element 49 is a bend in aforce dampening section 44 created by a pre-formed sheath 74 over aflexible tether 104. Alternatively the force redirecting element 49 canbe a bend in a force dampening section 44 made from a wire or tube withdesired flexibility incorporated into the force dampening section 44 bymeans of material selection and dimension. For example, the forcedampening section 44 can be made from Nitinol wire with a diameter ofabout 0.10 to 0.20 mm.

5. Force Dampening Section

As shown in FIGS. 16A to 16H, the force dampening section 44 comprises aflexible tubular structure 74. The flexible structure 74 can comprise ametal, a polymer, or a metal/polymer composite. The material andphysical features of the flexible structure 74 are selected so that theforce dampening section 44 has (1) sufficient flexibility to elasticallydeform when an energy delivery element 24 applies a pressure to an innerwall of a renal artery that is less than a pressure that is at high riskof causing trauma; but (2) sufficient stiffness to create a contactforce or pressure between the energy delivery element 24 and inner wallof the renal artery that allows for energy delivery and stable contact.The flexibility of the force dampening section 44 dampens the forceapplied by the energy delivery element 24 to the artery wall so that theforce remains in this suitable range as the deflectable section 34 isdeflected over a wide range. Furthermore, by elastically deforming, aforce dampening section 44 aligns an energy delivery element 24 so thatits side is in contact with the artery wall as previously discussed.

The material and physical features of the flexible structure 74 couldoptionally be selected so that the axial stiffness and torsionalstiffness of the flexible structure 74 is not greater than the axialstiffness and torsional stiffness of the third tubular structure 62. Theoverall flexibility of the flexible structure 74 could optionally be atleast equal to or greater than the flexibility of third tubularstructure 62 when the third tubular structure has not been deflected bythe control wire 40.

The flexible structure 74, as a part of the force dampening section 44,can be coupled to the deflectable section as described above.Alternatively, in embodiments that do not provide a deflectable section,the force dampening section can be coupled to the first flexure zone. Asshown in FIG. 16B, the energy delivery element 24 is carried at thedistal end of the flexible structure 74 for placement in contact withtissue along a vessel wall of a respective renal artery.

The material selected for the flexible structure 74 can be radiopaque ornon-radiopaque. For example, a radiopaque material, e.g., stainlesssteel, platinum, platinum iridium, or gold, can be used to enablevisualization and image guidance. When using a non-radiopaque material,the material optionally may be doped with a radiopaque substance, suchas barium sulfate, to facilitate visualization and image guidance.

The configuration of the flexible structure 74 can vary. For example, inthe embodiment depicted in FIG. 16B, the flexible structure 74 comprisesa thread 104 encased in, or covered with, a polymer coating or wrapping110. The thread 104 is routed through a proximal anchor 108, which isattached to the distal end of the deflectable section 34, and a distalanchor 106, which is fixed within or integrated into the heating element24/electrode 46. The distal anchor 106 may be fixed within the heatingelement 24/electrode 46 using, e.g., solder. Alternatively, the distalanchor 106 and heating element 24/electrode 46 may fabricated as asingle piece or unitary structure.

Although various types of materials can be used to construct theaforementioned structures, in order to have a flexible structure 74 thatsecurely connects to the deflectable section 34 and the energy deliveryelement 24, it is desirable for thread 104 to be comprised of Kevlar orsimilar polymer thread and for the proximal anchor 108 and distal anchor106 to be comprised of stainless steel. While the coating 110 can becomprised of any electrically insulative material, and particularlythose listed later with respect to sheath 80, it is desirable for thestructures of the flexible structure 74 to be encased/coated/covered bya low-durometer polymer such as carbothane laminate 110. As shown inFIG. 16B, one or more supply wires 29 may run alongside or within theflexible structure 74. As previously mentioned these wires may providethe energy delivery element 24 with electrical current/energy from thegenerator 26 and also convey data signals acquired by sensor 52. Asdepicted in FIG. 16B, the control wire 40 extending from the handleactuator 260 can be formed into the proximal anchor 108 and attached tothe elongated shaft using solder 130.

One advantage of the above-described configuration of the flexiblestructure 74 is that the flexible structure 74 creates a region ofelectrical isolation between the energy delivery element and the rest ofthe elongated shaft. Both the Kevlar thread 104 and laminate 110 areelectrically insulative, thereby providing the supply wire(s) 29 as thesole means for electrical connectivity. Accordingly, the externalsurface of the flexible structure 74 and force dampening section 44 iselectrically inactive.

As shown in FIGS. 16D through 16F, the flexible structure 74 allowsconsiderable passive deflection of the force dampening section 44 whenthe energy delivery element 24 is put into contact with the vessel wall.As already described, this flexibility has several potential benefits.One such benefit may be the ability of the force dampening section 44 toreduce force or stress applied between the energy delivery element 24and the vessel wall when or as the deflectable section 34 is deflected,relative to the force or stress that would be applied to the vessel wallduring deflectable section 34 deflection if the force dampening section44 were to be removed and the energy delivery element were to be coupleddirectly to the distal end of the deflectable section 34. This mayreduce a risk of trauma. Furthermore, the force or stress applied by theenergy delivery element 24 to the vessel wall may be maintained in aconsistent range during deflectable section 34 deflection, particularlyduring movement caused by respiration and/or pulsatile flow, which mayfacilitate consistent and/or controlled lesion creation.

The size and configuration of the flexible structure 74 enables theenergy delivery element to deflect in many directions because the forcedampening section may bend by angle Θ in any plane through the axis ofthe distal end region. For treatments within a peripheral blood vesselsuch as the renal artery, it is desirable that angle Θ≦90 degrees.Optionally, the flexible structure 74 is not very resilient, i.e., doesnot provide a significant restoring or straightening moment whendeflected. For embodiments having a distal assembly 53 that comprises aforce redirecting element 49, force dampening element 44 and energydelivery device 24 that are distal to a deflectable section, such as theembodiment shown in FIG. 7A, the distal assembly 53 can have a length ofless than about 10 mm, for example less than about 5 mm.

The energy delivery element 24 desirably may provide omni-directionaldelivery of energy in substantially any or all directions. As the forcedampening section 44 passively deflects at a treatment site about anangle θ appropriate to a given patient's anatomical geometry, anyportion of the energy delivery element 24 may be aligned with aninterior wall of the renal artery for energy delivery to target renalnerves. Blood flow may remove heat during such energy delivery, therebyreducing or mitigating a need for shielding or other preferentialdirecting of the energy delivered to the target renal nerves that couldmake the force dampening section 44 undesirably stiffer or bulkier. Suchomni-directional energy delivery without shielding/preferentialdirecting may facilitate simpler or safer positioning of the energydelivery element 24 at a treatment site, as compared to shielded ordirected energy delivery elements, e.g. energy delivery elementscomprising a microwave or radioactive power source.

In alternative embodiments of the force dampening section 44, theflexible structure 74 can take the form of a tubular metal coil, cable,braid, polymer or metal/polymer composite, as FIG. 16H shows.Alternatively, the flexible structure 74 can take the form of an oval,or rectangular, or flattened metal coil or polymer, as FIG. 16G shows.In alternate embodiments, the flexible structure 74 may comprise othermechanical structures or systems that allow the energy delivery element24 to pivot in at least one plane of movement. For example, the flexiblestructure 74 may comprise a hinge or ball/socket combination.

Candidate materials for the polymer material include polyethyleneterephthalate (PET); Pebax; polyurethane; urethane, carbothane,tecothane, low density polyethylene (LDPE); silicone; or combinationsthereof. The polymer material can be laminated, dip-coated,spray-coated, or otherwise deposited/applied over the flexible structure74. Alternatively, a thin film of the polymer material (e.g., PTFE) canbe wrapped about the flexible structure 74. Alternatively, the flexiblestructure 74 can be inherently insulated, and not require a separatesheath 80 or covering. For example, the flexible structure can comprisea polymer-coated coiled wire.

Optionally, force dampening section 44 can include a sensor 42 thatindicates an amount of deflection of force dampening section 44 as shownin FIG. 17A. The sensor 42 can be, for example, a piezo-resistiveelement that is a full or partial length of the force dampening section44 and can be mounted to a side of the force dampening section. A pairof conductors (not shown) running through the elongated shaft 16 wouldconnect the sensor 42 to an electrical supply and sensing circuit (notshown). When the force dampening section 44 is deflected in response toa force applied to the energy delivery element 24 or a portion of theforce dampening section 44 by an inner wall of a renal artery, thesensor 42 will deliver a signal that quantifies the amount ofdeflection. When the sensor 42 is a piezo-resistive element itsresistance will change proportional to its strain. The amount ofdeflection of force dampening section 44 is an indication of contactforce with the inner wall of the renal artery.

5. Rotation Controller

As will be discussed later in greater detail, it is desirable to rotatethe device within the renal artery after the energy delivery element isin contact with the vessel wall. However, it may be cumbersome andawkward for a clinical practitioner to rotate the entire handle assemblyat the proximal end of the device, particularly given the dimensions ofthe renal anatomy. In one representative embodiment, as shown in FIGS.17A and 17B, the proximal end of the shaft 16 is coupled to the handleassembly 200 by a rotator 230.

The proximal end of the force transmitting section 30 is attached to astationary coupling 88 on the rotator 230. Rotation of the rotator 230(as FIG. 17A shows) thereby rotates the force transmitting section 30,and, with it, the entire elongated shaft 16, without rotation of thehandle assembly 200. As FIG. 17A shows, a caregiver is thereby able tohold the proximal portion of the handle assembly 200 rotationallystationary in one hand and, with the same or different hand, apply atorsional force to the rotator 230 to rotate the elongated shaft 16.This allows the actuator to remain easily accessed for controlleddeflection.

Since there are cables and wires running from the handle assemblythrough the shaft of the device (e.g., control 40, electricaltransmission wire and/or sensor/thermocouple wire(s) 29, etc.), it isdesirable to limit rotation of the shaft relative to these wires inorder to avoid unnecessary entanglement and twisting of these wires. Arotational limiting element can be incorporated into the handle assemblyand rotator to address this issue. The rotator 230 and handle assemblycan be configured to allow for the optimal number of revolutions for theshaft, given such structural or dimensional constraints (e.g., wires).The components of the handle assembly may be configured, for example toallow for a finite number of revolutions of the shaft (e.g., two)independent of the handle assembly. Limiting rotation of the shaft tothe optimal number of revolutions may be achieved by any number ofcommonly known mechanical features.

As has been described and will be described in greater detail later, byintravascular access, the caregiver can manipulate the handle assembly200 to locate the distal end region 20 of the elongated shaft 16 withinthe respective renal artery. The caregiver can then operate the actuator260 on the handle assembly 200 (see FIGS. 17A and 17B) to deflect theenergy delivery element 24 about the deflectable section 34. Thecaregiver can then operate the rotator 230 on the handle assembly 200(see FIGS. 17A and 17B) to apply a rotational force along the elongatedshaft 16. The rotation of the elongated shaft 16 when the deflectablesection 34 is deflected within the respective renal artery rotates theenergy delivery element 24 within the respective renal artery, making iteasier to achieve contact with the vessel wall and determine whetherthere is wall contact, particularly in planes where there is poorangiographic visualization.

In an additional aspect of the disclosed technology, the handle assembly200 may be configured to minimize operator/caregiver handling of thedevice while it is within the patient. As shown, for example, in FIG.17B, the handle assembly also comprises one or more surfaces 243 thatsubstantially conform to the surface beneath (e.g., operating table).This surface 243, which is shown to be substantially flat in FIG. 17B,can alternatively be curved, shaped or angled depending on theconfiguration and/or geometry of the beneath surface. The conformingsurface 243 enables the clinical operator to keep the handle assembly200 stable when the treatment device 12 is within the patient. In orderto rotate the device when it is inside the patient, the operator cansimply dial the rotator 230 without any need to lift the handleassembly. When the operator desires to retract the device for subsequenttreatments, the operator can simply slide the handle assembly along thebeneath surface to the next position. Again, this mitigates the risk ofinjury due to operator error or over handling of the treatment device.Additionally or alternatively, the lower surface can engage the surfaceunderneath using clips, texture, adhesive, etc.

Additional enhancements to the rotation mechanism disclosed hereininclude providing tactile and/or visual feedback on the rotationalfitting so that the operator can exercise greater control and care inrotating the device. The rotator 230 can also be selectively locked tothe handle assembly, thereby preventing further rotation, if theoperator wishes to hold the treatment device in a particular angularposition. Another optional enhancement includes providing distancemarkers along the shaft/handle assembly to enable the operator to gaugedistance when retracting the treatment device.

B. Second Representative Embodiment (Deflectable Section Includes aForce Redirecting Element)

FIGS. 18A-19D show representative embodiments of the second embodimentwith an elongated shaft 16 that includes a force transmitting section30, first flexure zone 32, deflectable section 34, force redirectingelement 49, energy delivery element 24, and an optional force dampeningsection 44. In these embodiments, the materials, size, and configurationof the force transmitting section 30, first flexure zone 32, forceredirecting element 49 and optional force dampening section 44 arecomparable to their respective counterparts described in any of theprevious embodiments.

In these embodiments, however, the deflectable section 34 may comprise athird tubular structure 62 with a force redirecting element 49comprising a pre-formed shape or geometry that, in an unrestrainedconfiguration, is off-axis or deflected from the longitudinal axis ofthe elongated shaft 16 (see, e.g., FIGS. 18A and 18B), which mayfacilitate locating of the energy delivery element 24 into contact witha treatment site within a renal artery. The length and diameter ofdeflectable section 34 may be comparable to those described in any ofthe previous embodiments of the deflectable section 34. In oneembodiment, the pre-formed shape of the third tubular structure 62 maybe specified to provide the deflectable section 34 with a desired radiusof curvature RoC₂ and angle α2 (see FIG. 7C), such as those describedpreviously. In other embodiments, the pre-formed shape can take othergeometrical and dimensional forms. The third tubular structure 62 may befabricated, for example, from a shape memory material, such as anickel-titanium alloy (i.e., Nitinol) or from spring steel, to providethe pre-formed shape.

When advanced within, and retrieved from, a renal artery via anintravascular path, the deflectable section 34 may be positioned withina guide catheter, such as guide catheter 96, which may substantiallystraighten or constrain the third tubular structure 62 during suchintravascular delivery and retrieval. After advancement of thedeflectable section 34 distal of the guide catheter, the third tubularstructure 62 may re-assume its off-axis, pre-formed shape, e.g., tobring the energy delivery element 24 into contact with a wall of therenal artery. The deflectable section 34 optionally may be activelydeflected (e.g., as described previously via control wire 40 attached tohandle actuator 260), in addition to the passive deflection provided bythe pre-formed shape of the third tubular structure 62.

1. Active Deflection in the Direction of the Force Redirecting Element

When the deflectable section 34 is configured for both active andpassive deflection, the third tubular structure 62 may be configuredsuch that active deflection of the deflectable section is biased in thedirection of the third tubular structure's pre-formed shape. This can beachieved by making the third tubular structure 62 compressible in thedirection of the structure's pre-formed shape and resilient tocompression opposite the structure's pre-formed shape. In such aconfiguration, active deflection augments or magnifies the passivedeflection provided by the third tubular structure's pre-formed shape.

FIG. 18C provides a representative embodiment of a deflectable section34 that has a pre-formed shape and that is configured for activedeflection in the direction of the pre-formed shape. In FIG. 18C, thethird tubular structure 62 comprises a laser-cut pattern that includesspine 66 with connecting ribs 68. The spine 66 comprises a pre-formedshape that positions the deflectable section 34 off-axis or deflectedfrom the longitudinal axis of the elongated shaft 16 in an unrestrainedconfiguration. The direction of the pre-formed shape is such that thelaser-cut pattern biases active deflection of the third tubularstructure 62, in response to pulling on the control wire 40 coupled tothe distal end of the third tubular structure 62, toward the directionof the pre-formed shape. The control wire 40 is attached to a distal endof the deflectable section, for example, with solder 130.

2. Active Deflection in the Opposite Direction of the Force RedirectingElement for Bi-Directional Deflection Via a Single Control Wire

As an alternative to the embodiment of FIG. 18C, when the deflectablesection 34 is configured for both active and passive deflection, thethird tubular structure 62 may be configured such that active deflectionof the deflectable section is biased in about an opposite direction ofthe third tubular structure's pre-formed shape. This can be achieved bymaking the third tubular structure 62 compressible in the oppositedirection of the structure's pre-formed shape and resilient tocompression in the direction of the structure's pre-formed shape. Insuch a configuration, active deflection reduces or reverses the passivedeflection provided by the third tubular structure's pre-formed shape.

FIG. 18D provides a representative embodiment of a deflectable section34 that has a pre-formed shape and that is configured for activedeflection in the opposite direction of the pre-formed shape. In FIG.18D, the third tubular structure 62 again comprises a laser-cut patternthat includes spine 66 with connecting ribs 68. As in the embodiment ofFIG. 18C, the spine 66 comprises a pre-formed shape that positions thedeflectable section 34 off-axis or deflected from the longitudinal axisof the elongated shaft 16 in an unrestrained configuration. However, incontrast to the embodiment of FIG. 18C, the direction of the pre-formedshape is such that the laser-cut pattern biases active deflection of thethird tubular structure 62, in response to pulling on the control wire40 coupled to the distal end of the third tubular structure 62, awayfrom the direction of the pre-formed shape.

As seen in FIGS. 18E-18G, when the deflectable section 34 has apre-formed shape and is configured for active deflection in the oppositedirection of the pre-formed shape, the deflectable section desirably mayachieve bi-directional bending via a single control wire 40. As seen inFIG. 18E, in the unrestrained configuration of the deflectable section34 without active deflection (e.g., when the control wire 40 is notbeing pulled in tension), the deflectable section 34 assumes thepre-formed shape of its third tubular structure 62. As seen in FIG. 18F,tension applied to control wire 40 partially or completely straightensthe bend in the deflectable section 34. As seen in FIG. 18G, in someembodiments additional proximal tension (i.e. via pulling/proximalretraction) of control wire 40 may deflect the deflectable section inthe opposite direction of its pre-formed shape, thereby providingbi-directional bending of the deflectable section with a single controlwire 40.

Optionally, the control wire 40 may be under tension, as in FIG. 18F,during delivery and/or retrieval of the energy delivery element 24within a renal artery, in order to at least partially straighten thepre-formed shape of the deflectable section 34 during suchdelivery/retrieval. When positioned within the renal artery, tension maybe removed from the control wire 40 to deflect the deflectable sectionin the direction of its pre-formed shape, as in FIG. 18E, in order tobring the energy delivery element 24 into contact with a wall of therenal artery. Additionally or alternatively, the control wire 40 may bepulled more proximally to deflect the deflectable section in theopposite direction of its pre-formed shape, as in FIG. 18G, in order tobring the energy delivery element 24 into contact with an opposing wallof the renal artery without necessitating rotation of the elongatedshaft 16. As discussed previously, the force dampening section 44desirably accommodates contact with any wall of the renal artery andpassively deflects to bring the energy delivery element 24 into at leastpartial alignment with the contacted wall of the artery, therebyaccommodating bi-directional deflection of the deflectable section 34.

3. Active Deflection in any Desired Direction in Combination with theForce Redirecting Element

FIGS. 18C-18G illustrate representative embodiments of deflectablesection 34 that are configured for both active and passive deflection ofthe deflectable section, wherein the active deflection is either in thedirection of, or opposed to, the direction of passive deflection (i.e.,the direction of the force redirecting element's pre-formed shape).However, it should be understood that in other contemplated embodimentsactive deflection of the deflectable section may be in any plane(s), asdesired, and is not limited to active deflection in the direction ofpre-formed shape or in the opposite direction of pre-formed shape.

4. Active Deflection Longitudinally Offset from the Force RedirectingElement

In FIGS. 18C-18G, active deflection and passive deflection of thedeflectable section occur along a common longitudinal segment. Activeand passive deflection alternatively/additionally may be longitudinallyspaced or offset from one another. For example, the deflectable section34 may comprise a more proximal section that is configured for activedeflection and a more distal section that has a pre-formed shape, orvice versa. Active deflection may occur in the direction of thepre-formed shape, in the opposite direction of the pre-formed shape, orin any other direction, as desired.

FIG. 19A illustrates a representative embodiment of a deflectablesection 34 with a more proximal section configured for active deflectionand a more distal section that has a pre-formed shape. The more proximalsection of the deflectable section 34 illustratively is configured foractive deflection in the opposite direction of the more distal section'spre-formed shape. However, it should be understood that the pre-formedshape alternatively may be directed in the direction of activedeflection or in any other direction.

As seen in FIG. 19A, the third tubular structure 62 comprises alaser-cut pattern that includes spine 66 with connecting ribs 68. Incontrast to the embodiments of FIGS. 18A-18G, solder 130 connectscontrol wire 40 to the third tubular structure 62 proximal of thedeflectable section's distal end, e.g., at the distal end of a moreproximal section of the third tubular structure 62 and/or at theproximal end of a more distal section of the third tubular structure.Distal of the attachment of control wire 40 to the third tubularstructure 62, spine 66 comprises a force redirecting element 49, whichcomprises a pre-formed, off-axis shape. The third tubular structure'slaser-cut pattern biases active deflection of the third tubularstructure 62, in response to pulling on the control wire 40 coupled tothe third tubular structure 62 proximal of the spine's pre-formed shape,in the opposite direction of the pre-formed shape.

With reference now to FIGS. 19B-19D, when the deflectable section 34 hasa more proximal section configured for active deflection in an oppositedirection of a more distal section's pre-formed shape, the deflectablesection 34 desirably may promote buckling in the first flexure zone 32or deflectable section 34 with reduced contact force applied to thevessel wall by the energy delivery element 24 which may provide a moreatraumatic navigation. Additionally/alternatively, such a deflectablesection may facilitate the establishment of contact and treatment atangularly opposed luminal surfaces of the renal artery withoutnecessitating rotation of elongated shaft 16.

As seen in FIG. 19B, in the unrestrained configuration of thedeflectable section 34 without active deflection (e.g., when the controlwire 40 is not being pulled in tension), the more distal section of thedeflectable section 34 assumes the pre-formed shape of its third tubularstructure 62. As discussed previously, when positioned within a renalartery, the first flexure zone 32 may lie along or near a superior wallsurface of the renal artery (see, for example, FIG. 14A). As seen inFIG. 19C, when not actively deflected, the pre-formed shape of the moredistal section of the deflectable section may urge energy deliveryelement 24 and optional force dampening section 44 into contact withthat superior wall surface. Previously described passive deflection ofthe optional force dampening section may at least partially align theenergy delivery element 24 with the superior wall surface, as shown.

As seen in FIG. 19D, tension applied to control wire 40 deflects themore proximal section of the deflectable section 34 in the oppositedirection of the more distal pre-formed shape, e.g., toward an inferiorsurface of the renal artery. The pre-formed shape may cause the energydelivery element 24 to contact the inferior surface at a lower contactangle (i.e., at an angle less than perpendicular to the surface) than itotherwise would without the pre-formed shape. Previously describedpassive deflection of the optional force dampening section may at leastpartially align the energy delivery element 24 with the inferior wallsurface, as shown. FIGS. 19C and 19D illustrate establishment of contactand treatment at angularly opposed luminal surfaces of the renal arterywithout necessitating rotation of elongated shaft 16.

C. Third Representative Embodiment (Deflectable Section FacilitatesControlled, Multi-Directional Deflection)

FIGS. 20A-20D show representative embodiments of the third embodimenthaving an elongated shaft 16 that includes a force transmitting section30, a first flexure zone 32, a deflectable section 34, a forceredirecting element 49, energy delivery element 24 and an optional forcedampening section 44 (see FIG. 20A). In these embodiments, thematerials, size, and configuration of the force transmitting section 30,first flexure zone 32, and optional force dampening section 44 arecomparable to their respective counterparts described in any of theprevious embodiments. Furthermore, the length and diameter ofdeflectable section 34 in the embodiments of FIG. 20 may be comparableto those described in any of the previous embodiments of the deflectablesection 34. Also, controlled bending of the deflectable section 34 mayprovide the deflectable section with a desired radius of curvature RoC₂and angle α2 (see FIG. 7C), such as those described previously.

However, in the third embodiment of the present invention, thedeflectable section 34 may facilitate controlled deflection in multipledifferent directions, e.g., may comprise multiple control wires 40 forcontrollably deflecting the deflectable section in multiple differentdirections. Controlled, multi-directional bending of the deflectablesection may facilitate placement of energy delivery element 24 intostable contact with a treatment site or with multiple treatment siteswithin a renal artery. Such control over placement of the energydelivery element may be especially useful in patients with relativelytortuous vessels. For example, if placement of the energy deliveryelement 24 into contact with a renal arterial treatment site issub-optimal under controlled bending of the deflectable section in afirst direction, the deflectable section may be controllably deflectedin a second direction to more optimally place the energy deliveryelement into contact with the treatment site, or with an alternative oradditional treatment site. Furthermore, stable contact and energydelivery may be achievable at multiple treatment sites via controlledmulti-directional deflection of the deflectable section.

In some representative embodiments of the third embodiment, thedeflectable section may comprise a centrally positioned spine coupled toribs or surrounded by a coil; the centrally positioned spine may possessa geometry that facilitates controlled, multi-directional bending.

FIGS. 20B-20D provide representative embodiments of the third embodimentwith a deflectable section 34 configured for controlled,multi-directional bending having a central spine and multiple controlwires.

In the embodiment of FIGS. 20B and 20C, the deflectable section isconfigured for controlled, bi-directional bending. As seen in thecross-section of FIG. 16B, the third tubular structure 62 of thedeflectable section 34 comprises a centrally positioned spine 66 havinga substantially flat or ribbon shape (i.e., the spine's width issignificantly greater than its thickness) that substantially divides thethird tubular structure in half. A central lumen of diameter less thanthe spine's depth may be formed through the center of the spine 66 forpassage of electrical transmission wire(s) and/or sensor/thermocouplewire(s) 29.

Third tubular structure 62 may be fabricated, for example, viaElectrical Discharge Machining (EDM), micromachining and/or extrusion,to form a tube with a ribbon having a lumen, wherein the ribbon bisectsthe tube, as in FIG. 20B. As seen in FIG. 20C, a laser-cut pattern thenmay remove sections of the tube along its length to form connecting ribs68 a and 68 b at spaced intervals along the tube's length that extend onopposing sides of spine 66 about the circumference of the third tubularstructure 62. Control wires 40 a and 40 b are attached to a distal endof the deflectable section 34 with solder 130 on opposing sides of spine66 and travel along the length of the third tubular structure radiallypositioned between the spine 66 and the ribs 68.

Alternatively, the deflectable section 34 may comprise a centrallypositioned spine 66 that is resilient to compression and is surroundedby a third tubular structure 62. The third tubular structure iscompressible and may comprise a laser-cut hypo tube, a hollow coil witha loose pitch, a hollow cable, a braided shaft, etc. The spine may beconnected to the third tubular structure 62 along its length, may beconnected to the structure at only one or a few locations (e.g., at itsdistal end), or may float or be friction fit within the coiling thirdtubular structure.

The geometry of spine 66, in combination with the geometry of ribs 68 aand 68 b and the distal attachment locations of control wires 40 a and40 b, facilitate controlled, bi-directional bending of the deflectablesection 34, e.g., by substantially constraining bending of the spine 66in response to pulling of a wire 40 a or 40 b to planes perpendicular tothe width of the spine. The deflectable section deflects in a firstdirection in response to pulling on the control wire 40 a while thecontrol wire 40 b is not under significant tension (see FIG. 20C). Thedeflectable section deflects in a second, opposing direction in responseto pulling on the control wire 40 b while the control wire 40 a is notunder significant tension.

While FIGS. 20B and 20C illustrate a bi-directional bending embodimentof the deflectable section 34, the third tubular structure 62 may befabricated with a centrally positioned spine that facilitates bending inany number of directions, as desired. FIG. 20D illustrates an embodimentof a deflectable section with a centrally positioned spine that isconfigured for controlled, quad-directional deflection. As seen in FIG.20D, the third tubular structure 62 comprises centrally positionedspines 66 a and 66 b whose widths are angularly offset from one anotherby about 90° in an alternating pattern along the length of the thirdtubular structure. A centrally-positioned lumen extends through theribbon sections along the length of the third tubular structure forpassage of electrical transmission wire(s) and/or sensor/thermocouplewire(s) 29. Between each pair of the spinal ribbon sections 66 a and 66b, the spine 66 forms a spinal ribbon connector section 66 c thatconnects the pair of spinal ribbon sections.

Third tubular structure 62 thus comprises a series of repeating segmentsalong the length of the structure. Each repeating segment has a firstconnector section 66 c; followed lengthwise by a ribbon section 66 a;followed lengthwise by a second connector section 66 c; followedlengthwise by a ribbon section 66 b that is 90° angularly offset fromthe width of ribbon section 66 a; followed lengthwise by a repeatingfirst connector section 66 c; etc. The third tubular structure 62 ofFIG. 20D may, for example, be fabricated from a combination of EDM,micromachining and/or extrusion, as well laser cutting.

Control wires 40 a, 40 b, 40 c or 40 d are positioned within lumens thatextend through each ribbon section 66 a and 66 b near either end of thewidth of each ribbon section (i.e., four such lumens in all, in additionto the centrally-positioned lumen for passage of wire 29). Control wires40 a, 40 b, 40 c, and 40 d may be routed through these lumens along thelength of the third tubular structure and are attached to a distal endof the deflectable section with solder 130. Pulling on any one of thecontrol wires while the other three control wires are not undersignificant tension may provide controlled deflection of the deflectablesection 34 in the direction of the wire being pulled. In this manner,the deflectable section 34 may be configured for controlled,quad-directional bending in four directions that are about 90° angularlyoffset or out of phase from one another.

FIGS. 20B and 20C illustrate a deflectable section 34 with a centrallypositioned spine 66 configured for bi-directional controlled deflection,while FIG. 20D illustrates a deflectable section 34 with a centrallypositioned spine 66 configured for quad-directional controlleddeflection. The deflectable section alternatively may comprise acentrally positioned spine 66 configured for deflection in any number ofadditional directions, as desired. For example, additional ribbonsections may be provided at additional angular offsets and connected byspinal connector sections having additional sides. When combined withappropriate ribs 68 and control wires 40, controlled deflection in anynumber of directions may be achieved.

D. Fourth Representative Embodiment (Deflectable Section Configured forDeflection at a Joint)

FIGS. 21A-21C show representative embodiments of the fourth embodimenthaving an elongated shaft 16 that includes a force transmitting section30, a first flexure zone 32, a deflectable section that comprises ajoint 35, and a force dampening section 44 comprising a forceredirecting element 49 (see FIG. 21A). In these embodiments, thematerials, size, and configuration of the force transmitting section 30,first flexure zone 32, force dampening section 44, and force redirectingelement 49 are comparable to their respective counterparts described inany of the previous embodiments.

However, in the fourth embodiment of the present invention, thedeflectable section 34 is replaced by one or more joints 35 tofacilitate deflection of the force dampening section 44. Joints 35 mayprovide precise deflection control, as the joints may exhibit consistentdeflection dynamics. Furthermore, joints may provide a sharper bend thanwould be achievable with some of the previously described embodiments ofthe deflectable section since a joint represents a pivot point asopposed to a Radius of Curvature. Thus, the length of a jointeddeflectable section may be less than the length of a previouslydescribed biased spine deflectable section. This may facilitate thermalneuromodulation in shorter renal arteries, and/or may facilitate use ofa longer force dampening section 44 as shown in FIG. 21C. A longer forcedampening section may dissipate vessel contact force over its longerlength and resiliently apply pressure to the vessel wall to providestable electrode contact during pulsatile blood flow and respiratorymotion. Also, a longer force dampening section may be easier tovisualize with fluoroscopy. The force dampening section 44 may bebetween about 6 mm and 16 mm long, for example about less than or equalto 9.5 mm, which could be suitable to provide sufficient flexure inrenal arteries.

With reference to FIG. 21B, in one representative embodiment of thefourth embodiment, hinge joint 35 connects the first flexure zone 32 tothe force dampening section 44. Control wires 40 a and 40 b are attachedto either side of the joint 35 distal to the Axis of Rotation R forrotating the force dampening section 44 about the Axis of Rotation R ofthe hinge joint. Alternatively, one control wire is attached to a sideof a joint 35 distal to the Axis of Rotation R for rotating the forcedampening section 44 about the Axis of Rotation R of the hinge joint anda spring rotates the force dampening section 44 back to its undeflectedstate when tension in the control wire is relieved.

Force dampening section 44 comprises, along its longitudinal length, aforce redirecting element 49, which distances the energy deliveryelement 24 from the axis of the force dampening section 44 at a similarangle and distance as described in earlier embodiments. Since theslenderness ratio (length:diameter) is greater for a longer forcedampening section 44, a longer force dampening section 44 is moresusceptible to buckling especially when a load applied is distanced fromits axis. As the distal assembly 53 is advanced into a renal artery andthe energy delivery element 24 contacts a renal artery wall, the loadapplied to the energy delivery element 24 is distanced from the axis ofthe force dampening section 44 and could cause the force dampeningsection 44 to buckle at a load that is lower than a traumatic load. Aforce redirecting element 49 can be located on the force dampeningsection 44 longitudinally at about the midpoint. For example, on a 9.5mm long force dampening section 44 the force redirecting element 49 canbe about 4 to 5 mm proximal to the distal end.

E. Fifth Representative Embodiment (the Force Redirecting Element isConfigured to Facilitate Multi-Directional Access)

FIGS. 22A-22G show representative embodiments of the fifth embodimenthaving an elongated shaft 16 that includes a force transmitting section30, a first flexure zone 32, and a force dampening section 44 comprisinga force redirecting element. In these embodiments, the materials, size,and configuration of the force transmitting section 30, first flexurezone 32, force dampening section 44, force redirecting elements 49, andenergy delivery element 24 are comparable to their respectivecounterparts described in any of the previous embodiments.

However, in the fifth representative embodiment the force dampeningsection 44 and force redirecting element 49 are configured to deflectthe energy delivery element 24 in multiple directions so that the energydelivery element 24 can be placed in contact with an inner wall of arenal artery at various locations. In such embodiments, the forceredirecting element 49 comprises multiple (i.e., more than one) bends.For example, as shown in FIG. 22D, bends 49′ and 49″ are spaced apartalong the axis of the catheter. The fifth embodiment is configured to beadvanced into a renal artery while retracted in a delivery sheath 95.When the distal assembly is retracted in the delivery sheath the forcedampening section 44 and force redirecting element 49 flexibly conformto the delivery sheath (see FIG. 22B). When the distal assembly isadvanced to a desired depth in a renal artery the delivery sheath ispulled back to expose a first bend 49′ of the force redirecting element49 which elastically deforms to deflect the force dampening section 44 afirst angle α8, distancing and energy delivery element 24 from the axisof the elongated tubular body 16 in a first direction (see FIG. 22C).When the delivery sheath is pulled back further to expose a second bend49″ the second bend elastically deforms deflecting the force dampeningsection 44 a second angle α9, distancing the energy delivery element 24from the axis of the elongated tubular body 16 in a second direction(see FIG. 22D).

The force redirecting element 49 can be configured with multiple anglesα8 and α9 as shown in FIG. 22A such that when deployed in a renal arteryan energy delivery element 24 is placed in contact with an inner wall ofa renal artery in multiple directions dependant on the portion of theforce redirecting element 49 that protrudes from a delivery sheath asshown in FIGS. 22E and 22F. The angles α8 and α9 can be greater than 90°and less than 180° and such that a first angle α8 minus a second angleα9 is greater than 0° and less than 90°, for example first angle α8 canbe between about 130° and 150°, for example less than or equal to 140°,and second angle α9 can be between about 90° and 130°, for example lessthan or equal to about 110°. The length of the force dampening section44 and position of the force redirecting element 49 are configured sothat the energy delivery element 24 is placed in contact with an innerwall of a renal artery with stable contact force. For example, thelength from the distal end of an energy delivery element 24, includingthe force dampening section 44 to the first bend 49′ can be about 8 mmto 11 mm (e.g. less than or equal to 9.5 mm); the first angle α8 can beabout 130° to 150° (e.g. less than or equal to 140°); the length betweenthe first and second angle can be about 1.25 mm to 3 mm (e.g. less thanor equal to 1.5 mm); and the second angle α9 can be about 90° to 130°(e.g. less than or equal to 110°).

Alternatively, force redirecting element 49 can be configured with agradual curve such as a helical shape as shown in FIG. 22G such theforce dampening section 44 is deflected in multiple three dimensionaldirections, depending on the proportion of force redirecting element 49that is protruded from a delivery sheath. The force redirecting element49 in combination with the force dampening section 44 are configuredsuch that as the force redirecting element 49 is advanced from adelivery sheath in its flexibly conformed retracted state it elasticallydeforms to place an energy delivery element 24, mounted on a distal endof the force dampening section 44, in contact with an inner wall of arenal artery. For example, the force redirecting element 49 can comprisea helical structure with a helical angle between about 20° and 50° (e.g.less than or equal to 30°); a diameter of about 2 mm to 4 mm (e.g. lessthan or equal to 3 mm); and about 0.5 to 3 turns (e.g. less than orequal to 1 turn); and the force redirecting element 49 can be positionedabout 7 mm to 11 mm (e.g. less than or equal to 9.5 mm) from the distalend of the energy delivery element 24.

F. Sixth Representative Embodiment (the Length of the Force DampeningSection can be Telescopically Adjusted)

FIGS. 23A-23D show representative embodiments of the sixth embodimenthaving an elongated shaft 16 that includes a force transmitting section30, a first flexure zone 32, a force redirecting element 49, and a forcedampening section 44. In these embodiments, the materials, size, andconfiguration of the force transmitting section 30, first flexure zone32, force redirecting element 49, force dampening section 44, and energydelivery element 24, are comparable to their respective counterpartsdescribed in any of the previous embodiments.

However, in the sixth representative embodiment the force redirectingelement 49 is connected to a first flexure zone 32 and the forcedampening section 44 comprises an elongated flexible wire or tube thatis slidably contained in a lumen 17 passing through the forceredirecting element 49 and elongated tubular body 16 such that the forcedampening section 44 can be telescopically distanced from the distalopening of the lumen 17 by advancing the proximal end of the forcedampening section 44 through the lumen 17. As with previous embodimentsthe force redirecting element 49 is configured to flexibly conform tothe inner lumen of a guide catheter and elastically deflect to apredetermined angle when not constrained by the guide catheter. Theforce redirecting element 49 comprises an angle as discussed earlierthat distances the energy delivery element 24 from the axis of theelongated tubular body 16 such that as the catheter is advanced along anaxial trajectory and a force is applied to the energy delivery element24 by a contacting inner artery wall, the force dampening section 44 andelongated tubular body are persuaded to buckle and the trajectory ismodified to flow through an artery. The telescopically adjustable lengthof the force dampening section 44 can be shortened while the distalassembly 53 is being advanced through a renal artery. When the distalassembly is advanced to a desired distance in a renal artery the forcedampening section 44 can be telescopically lengthened to facilitatecontact between the energy delivery element 24 and an inner wall of therenal artery.

The force redirecting element 49 can deflect the force dampening section44 at angle similar to an angle in previous embodiments (such as angleα4 shown in FIG. 7B). For example, the angle of the force redirectingelement 49 can be between about 130° and 170° (e.g. less than or equalto 160°). The minimum length of the force dampening section 44protruding distal from the bend of the force redirecting element 49 canalso be similar to the length L4 of a force dampening section 44 inprevious embodiments (as shown in FIG. 7A). For example, the minimumprotruding length of the force dampening section 44 can be between about2 mm and 5 mm. The length of the force dampening section 44 protrudingfrom the distal opening of the lumen 17 can be telescopically increasedto a maximum of between about 5 mm to 30 mm (e.g. less than or equal to20 mm). Alternatively, a combination of the angle α4 and length of thetelescopically protruding force dampening section 44 can distance anenergy delivery element 24 from the axis of the elongated tubular body16 by a distance of between about 1 mm and 15 mm.

As shown in FIG. 23D force dampening section 44 can further comprise asecond force redirecting element 49′ that distances the distal tip ofthe energy delivery element 24 from the axis of the force dampeningsection 44 such that as the force dampening section 44 is telescopicallyadvanced, a load created by contact with the artery is distanced fromthe axis of the force dampening section 44 promoting buckling of theforce dampening section 44.

Force dampening section 44 can be comprised, for example, of aelectrically insulated Nitinol wire and conducting wires that carryenergy and sensor signals to and from the energy delivery element 24 andthe generator 26 can be held in the space between the electricalinsulation and the Nitinol wire. The proximal end of the force dampeningsection 44 can extend through a lumen to a proximal opening in the lumenof the elongated tubular body where it can be manipulated totelescopically lengthen the distal portion of the force dampeningsection 44 that protrudes from the distal opening of the lumen 17.Alternatively, the proximal end of the force dampening section 44 can bemanipulated by an actuator 260 in a handle 200.

IV. USE OF THE SYSTEM A. Intravascular Delivery, Deflection andPlacement of the Treatment Device

Any one of the embodiments of the treatment devices 12 described hereincan be delivered over a guide wire using conventional over-the-wiretechniques. When delivered in this manner (not shown), the elongatedshaft 16 includes a passage or lumen accommodating passage of a guidewire.

Alternatively, any one of the treatment devices 12 described herein canbe deployed using a conventional guide catheter or pre-curved renalguide catheter 94.

When using a guide catheter 94 (see FIG. 6A), the femoral artery isexposed and cannulated at the base of the femoral triangle, usingconventional techniques. In one exemplary approach, a guide wire (notshown) is inserted through the access site and passed using imageguidance through the femoral artery, into the iliac artery and aorta,and into either the left or right renal artery. A guide catheter can bepassed over the guide wire into the accessed renal artery. The guidewire is then removed. Alternatively, a renal guide catheter (shown inFIG. 24A), which is specifically shaped and configured to access a renalartery, can be used to avoid using a guide wire. Still alternatively,the treatment device can be routed from the femoral artery to the renalartery using angiographic guidance and without the need of a guidecatheter.

When a guide catheter is used, at least three delivery approaches can beimplemented. In one exemplary approach, one or more of theaforementioned delivery techniques can be used to position a guidecatheter within the renal artery just distal to the entrance of therenal artery. The treatment device is then routed via the guide catheterinto the renal artery. Once the treatment device is properly positionedwithin the renal artery, the guide catheter is retracted from the renalartery into the abdominal aorta. In this approach, the guide cathetershould be sized and configured to accommodate passage of the treatmentdevice. For example, a 6 French guide catheter can be used.

In a second exemplary approach, a first guide catheter is placed at theentrance of the renal artery (with or without a guide wire). A secondguide catheter is passed via the first guide catheter (with or withoutthe assistance of a guide wire) into the renal artery. The treatmentdevice is then routed via the second guide catheter into the renalartery. Once the treatment device is properly positioned within therenal artery the second guide catheter is retracted, leaving the firstguide catheter at the entrance to the renal artery. In this approach thefirst and second guide catheters should be sized and configured toaccommodate passage of the second guide catheter within the first guidecatheter (i.e., the inner diameter of the first guide catheter should begreater than the outer diameter of the second guide catheter). Forexample, the first guide catheter could be 8 French in size and thesecond guide catheter could be 5 French in size.

In a third exemplary approach, and as shown in FIG. 24A, a renal guidecatheter 94 is positioned within the abdominal aorta, just proximal tothe entrance of the renal artery. As now shown in FIG. 24B, thetreatment device 12 as described herein is passed through the guidecatheter 94 and into the accessed renal artery. The elongated shaftmakes atraumatic passage through the guide catheter 94, in response toforces applied to the force transmitting section 30 through the handleassembly 200. The first flexure zone 32 accommodates significant flexureat the junction of the left/right renal arteries and aorta to gain entryinto the respective left or right renal artery through the guidecatheter 94 (as FIG. 24B shows).

As FIG. 24C shows, the deflectable section 34 on the distal end portionof the elongated shaft 16 can now be axially translated into therespective renal artery, remotely deflected (illustratively, planardeflection or bending, but alternatively any other previously describeddeflection may be provided) and/or rotated in a controlled fashionwithin the respective renal artery to attain proximity to and a desiredalignment with an interior wall of the respective renal artery. As FIG.24C further shows, the optional force dampening section 44 bends toplace the thermal energy heating element 24 into contact with tissue onthe interior wall (alternatively or additionally, one or more energydelivery elements 24 may positioned along the length of the deflectablesection 34 and brought into contact with tissue on the interior wallduring remote deflection of the deflectable section).

B. Creation of Thermally Affected Tissue Regions

As previously described (and as FIG. 24B shows), the energy deliveryelement 24 can be positioned by bending along the first flexure zone 32at a first desired axial location within the respective renal artery. AsFIG. 24C shows, the energy delivery element 24 can be radiallypositioned by deflection of deflectable section 34 toward the vesselwall. As FIG. 24C also shows, the energy delivery element 24 can beplaced into a condition of optimal surface area contact with the vesselwall by further deflection of the force dampening section 44.

Once the energy delivery element 24 is positioned in the desiredlocation by a combination of deflection of the deflectable section 34,deflection of the force dampening section 44 and/or rotation of thecatheter, treatment can be administered. Optionally, infusate, such assaline, may be delivered (e.g., may be infused through the energydelivery element) in the vicinity of the treatment site before, duringand/or after treatment to provide conductive and/or convective coolingin excess of that provided by blood flow. By applying energy through theenergy delivery element 24, a first thermally affected tissue region98(a) can be formed, as FIG. 24D shows. In the illustrated embodiment,the thermally affected region 98(a) takes the form of a lesion on thevessel wall of the respective renal artery.

After forming the first thermally affected tissue region 98(a), thecatheter optionally may be repositioned for another thermal treatment.As described above in greater detail, it is desirable to create multiplefocal lesions that are circumferentially spaced along the longitudinalaxis of the renal artery. To achieve this result, the catheteroptionally may be retracted and, optionally, rotated to position theenergy delivery element proximally along the longitudinal axis of theblood vessel. Rotation of the elongated shaft 16 from outside the accesssite (see FIG. 24E) may circumferentially reposition the energy deliveryelement 24 about the renal artery. Once the energy delivery element 24is positioned at a second axial and circumferential location within therenal artery spaced from the first-described axial position, as shown inFIG. 24E (e.g., 98(b)), another focal treatment can be administeredtreatment (with or without saline infusion). By repeating themanipulative steps just described (as shown in FIGS. 24F through 24K),the caregiver can create several thermally affected tissue regions98(a), 98(b), 98(c) and 98(d) on the vessel wall that are axially andcircumferentially spaced apart, with the first thermally affected tissueregion 98(a) being the most distal and the subsequent thermally affectedtissue regions being more proximal. FIG. 24I provides a cross-sectionalview of the lesions formed in several layers of the treated renalartery. This figure shows that several circumferentially and axiallyspaced-apart treatments (e.g., 98(a)-98(d)) can provide substantialcircumferential coverage and, accordingly, cause a neuromodulatoryeffect to the renal plexus. Clinical investigation indicates that eachlesion will cover approximately 30 percent of the circumferential areasurrounding the renal artery. In other embodiments, the circumferentialcoverage of each lesion can be as much as 60 percent.

In an alternative treatment approach, the treatment device can beadministered to create a complex pattern/array of thermally affectedtissue regions along the vessel wall of the renal artery. As FIG. 24Lshows, this alternative treatment approach provides for multiplecircumferential treatments at each axial site (e.g., 98, 99 and 101)along the renal artery. Increasing the density of thermally affectedtissue regions along the vessel wall of the renal artery using thisapproach might increase the probability of thermally-blocking the neuralfibers within the renal plexus.

The rotation of the energy delivery element 24 within the renal arteryas shown in FIG. 24G may improve the reliability and consistency of thetreatment. Since angiographic guidance such as fluoroscopy only providesvisualization in two dimensions, it is generally only possible in theanterior/posterior view to obtain visual confirmation of wall contact atthe superior (vertex) and inferior (bottom) of the renal artery. Foranterior and posterior treatments, it may be desirable to first obtainconfirmation of contact at a superior or inferior location and thenrotate the catheter such that the energy delivery element travelscircumferentially along the vessel wall until the desired treatmentlocation is reached. Physiologic data such as impedance can beconcurrently monitored to ensure that wall contact is maintained oroptimized during catheter rotation. Alternatively, the C-arm of thefluoroscope can be rotated to achieve a better angle for determiningwall contact.

FIG. 24 illustrate multiple longitudinally and circumferentially spacedfocal lesions that are created by repositioning energy delivery element24 through a combination of deflectable section deflection, andelongated shaft rotation and/or translation. In some of the previouslydescribed embodiments of the treatment device, such multiple focallesions may be created with multiple energy delivery elements 24positioned along the length of the distal end region 20. Additionally oralternatively, in some of the previously described embodiments of thetreatment device, such multiple focal lesions may be created byrepositioning energy delivery element(s) 24 solely through deflectablesection deflection in multiple planes, solely through elongated shafttranslation, solely through elongated shaft rotation, or solely throughany subset of deflectable section deflection, elongated shafttranslation and elongated shaft rotation.

FIGS. 27A to 27C provide fluoroscopic images of a treatment device,similar to the one shown in FIG. 5 but without a force redirectingelement 49, within a renal artery during an animal study. FIG. 27A showspositioning of the treatment device and energy delivery element 24 at adistal treatment location. The deflectable section 34 has been deflectedto position the energy delivery element 24 in contact with the vesselwall and to cause flexure in the force dampening section 44. FIG. 27Aalso shows contact region 124 where the apex of the bend of thedeflectable section 34 is in contact with the vessel wall in radial orangular opposition to contact between the energy delivery element andvessel wall. FIG. 27B shows the placement of the treatment device at amore proximal treatment location following circumferential rotation andaxial retraction. FIG. 27C shows the placement of the treatment deviceat a proximal treatment location just distal to the junction of theaorta and renal artery. FIGS. 27D and 27E provide analogous fluoroscopicimages depicting the treatment device, similar to the one shown in FIG.5 but without a force redirecting element 49, positioned for treatmentwithin a human renal artery. FIG. 27D shows the treatment deviceadvanced to a distal treatment location similar to that described abovewith respect to FIG. 27A. FIG. 27E shows the treatment device in aproximal treatment position similar to that described above with respectto FIG. 27C.

Experience using the treatment device of FIGS. 27A to 27E revealed thatthe treatment device preformed the desired functions of for (i)percutaneous introduction into a femoral or brachial artery through asmall-diameter access site; (ii) atraumatic passage through the tortuousintravascular path through an iliac artery, into the aorta, and into arespective left/right renal artery, including (iii) accommodatingsignificant flexure at the junction of the left/right renal arteries andaorta to gain entry into the respective left or right renal artery; (iv)accommodating controlled translation, deflection, and/or rotation withinthe respective renal artery to attain proximity to and a desiredalignment with an interior wall of the respective renal artery; (v)allowing the placement of at least one energy delivery element intocontact with tissue on the interior wall in an orientation thatoptimizes the active surface area of the energy delivery element; and(vi) allowing substantially stable contact force between the at leastone energy delivery element and the interior wall during motion of therenal artery with respect to the aorta due to respiration and/or bloodflow pulsatility.

However, experience using the treatment device of FIGS. 27A to 27E alsorevealed that the functions of (iv), (v), and (vi) could be improved bymodifying the treatment device to have a force redirecting element asdescribed in the present application, particularly when used in renalarteries with greater degrees of tortuousity.

Since both the energy delivery element 24 and solder 130 at the distalend of the deflectable section 34 can be radiopaque, as shown in FIGS.27A to 27C, the operator using angiographic visualization can use theimage corresponding to the first treatment location to relativelyposition the treatment device for the second treatment. For example, inrenal arteries of average length, it is desirable for the clinicaloperator to treat at about every 5 mm along the length of the mainartery. In embodiments where the length of the force dampening section44 is 5 mm, the operator can simply retract the device such that thecurrent position of the energy delivery element 24 is longitudinallyaligned with the position of the solder 130 in the previous treatment.

In another embodiment, a different type of radiopaque marker can replacesolder 130. For example, a band of platinum can be attached to thedistal end of the deflectable section to serve as a radiopaque marker.

Since angiographic visualization of the vasculature generally requirescontrast agent to be infused into the renal artery, it may be desirableto incorporate within or alongside the treatment device a lumen and/orport for infusing contrast agent into the blood stream. Alternatively,the contrast agent can be delivered into the blood alongside thetreatment device within the annular space between the treatment deviceand the guide catheter through which the device is delivered.

Exposure to thermal energy (heat) in excess of a body temperature ofabout 37° C., but below a temperature of about 45° C., may inducethermal alteration via moderate heating of the target neural fibers orof vascular structures that perfuse the target fibers. In cases wherevascular structures are affected, the target neural fibers are deniedperfusion resulting in necrosis of the neural tissue. For example, thismay induce non-ablative thermal alteration in the fibers or structures.Exposure to heat above a temperature of about 45° C., or above about 60°C., may induce thermal alteration via substantial heating of the fibersor structures. For example, such higher temperatures may thermallyablate the target neural fibers or the vascular structures. In somepatients, it may be desirable to achieve temperatures that thermallyablate the target neural fibers or the vascular structures, but that areless than about 90° C., or less than about 85° C., or less than about80° C., and/or less than about 75° C. Regardless of the type of heatexposure utilized to induce the thermal neuromodulation, a reduction inrenal sympathetic nerve activity (“RSNA”) is expected.

D. Control of Applied Energy

With the treatments disclosed herein for delivering therapy to targettissue, it may be beneficial for energy to be delivered to the targetneural structures in a controlled manner. The controlled delivery ofenergy will allow the zone of thermal treatment to extend into the renalfascia while reducing undesirable energy delivery or thermal effects tothe vessel wall. A controlled delivery of energy may also result in amore consistent, predictable and efficient overall treatment.Accordingly, the generator 26 desirably includes programmed instructionscomprising an algorithm 102 (see FIG. 5) for controlling the delivery ofpower and energy to the thermal heating device. The algorithm 102, arepresentative embodiment of which is shown in FIG. 25, can beimplemented as a conventional computer program for execution by aprocessor coupled to the generator 26. A caregiver using step-by-stepinstructions can also implement the algorithm 102 manually.

The operating parameters monitored in accordance with the algorithm mayinclude, for example, temperature, time, impedance, power, flowvelocity, volumetric flow rate, blood pressure, heart rate, etc.Discrete values in temperature may be used to trigger changes in poweror energy delivery. For example, high values in temperature (e.g. 85degrees C.) could indicate tissue desiccation in which case thealgorithm may decrease or stop the power and energy delivery to preventundesirable thermal effects to target or non-target tissue. Timeadditionally or alternatively may be used to prevent undesirable thermalalteration to non-target tissue. For each treatment, a set time (e.g., 2minutes) is checked to prevent indefinite delivery of power.

Impedance may be used to measure tissue changes. Impedance indicates theelectrical property of the treatment site. If a thermal inductive,electric field is applied to the treatment site the impedance willdecrease as the tissue cells become less resistive to current flow. Iftoo much energy is applied, tissue desiccation or coagulation may occurnear the electrode, which would increase the impedance as the cells losewater retention and/or the electrode surface area decreases (e.g., viathe accumulation of coagulum). Thus, an increase in tissue impedance maybe indicative or predictive of undesirable thermal alteration to targetor non-target tissue.

Additionally or alternatively, power is an effective parameter tomonitor in controlling the delivery of therapy. Power is a function ofvoltage and current. The algorithm may tailor the voltage and/or currentto achieve a desired power.

Derivatives of the aforementioned parameters (e.g., rates of change)also may be used to trigger changes in power or energy delivery. Forexample, the rate of change in temperature could be monitored such thatpower output is reduced in the event that a sudden rise in temperatureis detected. Likewise, the rate of change of impedance could bemonitored such that power output is reduced in the event that a suddenrise in impedance is detected.

As seen in FIG. 25, when a caregiver initiates treatment (e.g., via thefoot pedal), the algorithm 102 commands the generator 26 to graduallyadjust its power output to a first power level P₁ (e.g., 5 watts) over afirst time period t₁ (e.g., 15 seconds). The power increase during thefirst time period is generally linear. As a result, the generator 26increases its power output at a generally constant rate of P₁/t₁.Alternatively, the power increase can be non-linear (e.g., exponentialor parabolic) with a variable rate of increase. Once P₁ and t₁ areachieved, the algorithm can hold at P₁ until a new time t₂ for apredetermined period of time t₂-t₁ (e.g., 3 seconds). At t₂ power isincreased by a predetermined increment (e.g., 1 watt) to P₂ over apredetermined period of time, t₃-t₂ (e.g., 1 second). This power ramp inpredetermined increments of about 1 watt over predetermined periods oftime can continue until a maximum power P_(MAX) is achieved or someother condition is satisfied. In one embodiment, P_(MAX) is 8 watts. Inanother embodiment P_(MAX) is 10 watts. Optionally, the power may bemaintained at the maximum power P_(MAX) for a desired period of time orup to the desired total treatment time (e.g., up to about 120 seconds).

In FIG. 25, algorithm 102 illustratively comprises a power-controlalgorithm. However, it should be understood that algorithm 102alternatively may comprise a temperature-control algorithm. For example,power may be gradually increased until a desired temperature (ortemperatures) is obtained for a desired duration (durations). In anotherembodiment, a combination power-control and temperature-controlalgorithm may be provided.

As discussed, the algorithm 102 includes monitoring certain operatingparameters (e.g., temperature, time, impedance, power, flow velocity,volumetric flow rate, blood pressure, heart rate, etc.). The operatingparameters can be monitored continuously or periodically. The algorithm102 checks the monitored parameters against predetermined parameterprofiles to determine whether the parameters individually or incombination fall within the ranges set by the predetermined parameterprofiles. If the monitored parameters fall within the ranges set by thepredetermined parameter profiles, then treatment can continue at thecommanded power output. If monitored parameters fall outside the rangesset by the predetermined parameter profiles, the algorithm 102 adjuststhe commanded power output accordingly. For example, if a targettemperature (e.g., 65 degrees C.) is achieved, then power delivery iskept constant until the total treatment time (e.g., 120 seconds) hasexpired. If a first temperature threshold (e.g., 70 degrees C.) isachieved or exceeded, then power is reduced in predetermined increments(e.g., 0.5 watts, 1.0 watts, etc.) until a target temperature isachieved. If a second power threshold (e.g., 85 degrees C.) is achievedor exceeded, thereby indicating an undesirable condition, then powerdelivery can be terminated. The system can be equipped with variousaudible and visual alarms to alert the operator of certain conditions.

The following is a non-exhaustive list of events under which algorithm102 may adjust and/or terminate/discontinue the commanded power output:

(1) The measured temperature exceeds a maximum temperature threshold(e.g., about 70 degrees to about 85 degrees C.).

(2) The average temperature derived from the measured temperatureexceeds an average temperature threshold (e.g., about 65 degrees C.).

(3) The rate of change of the measured temperature exceeds a rate ofchange threshold.

(4) The temperature rise over a period of time is below a minimumtemperature change threshold while the generator 26 has non-zero output.Poor contact between the energy delivery element 24 and the arterialwall can cause such a condition.

(5) A measured impedance exceeds an impedance threshold (e.g., <20 Ohms,or >500 Ohms).

(6) A measured impedance exceeds a relative threshold (e.g., impedancedecreases from a starting or baseline value and then rises above thisbaseline value)

(7) A measured power exceeds a power threshold (e.g., >8 Watts or >10Watts).

(8) A measured duration of power delivery exceeds a time threshold(e.g., >120 seconds).

V. PREPACKAGED KIT FOR DISTRIBUTION, TRANSPORT AND SALE OF THE DISCLOSEDAPPARATUSES AND SYSTEMS

As shown in FIG. 26, one or more components of the system 10 shown inFIG. 5 can be packaged together for convenient delivery to and use bythe customer/clinical operator. Components suitable for packaginginclude, the treatment device 12, the cable 28 for connecting thetreatment device 12 to the generator 26, the neutral or dispersiveelectrode 38, and one or more guide catheters 94 (e.g., a renal guidecatheter). Cable 28 can also be integrated into the treatment device 12such that both components are packaged together. Each component may haveits own sterile packaging (for components requiring sterilization) orthe components may have dedicated sterilized compartments within the kitpackaging. This kit may also include step-by-step instructions for use126 that provide the operator with technical product features andoperating instructions for using the system 10 and treatment device 12,including all methods of insertion, delivery, placement and use of thetreatment device disclosed herein.

VI. ADDITIONAL CLINICAL USES OF THE DISCLOSED APPARATUSES, METHODS ANDSYSTEMS

Although much of the disclosure in this Specification relates to atleast partially denervating a kidney of a patient to block afferentand/or efferent neural communication from within a renal blood vessel(e.g., renal artery), the apparatuses, methods and systems describedherein may also be used for other intravascular treatments. For example,the aforementioned catheter system, or select aspects of such system,can be placed in other peripheral blood vessels to deliver energy and/orelectric fields to achieve a neuromodulatory affect by altering nervesproximate to these other peripheral blood vessels. There are a number ofarterial vessels arising from the aorta which travel alongside a richcollection of nerves to target organs. Utilizing the arteries to accessand modulate these nerves may have clear therapeutic potential in anumber of disease states. Some examples include the nerves encirclingthe celiac trunk, superior mesenteric artery, and inferior mesentericartery.

Sympathetic nerves proximate to or encircling the arterial blood vesselknown as the celiac trunk may pass through the celiac ganglion andfollow branches of the celiac trunk to innervate the stomach, smallintestine, abdominal blood vessels, liver, bile ducts, gallbladder,pancreas, adrenal glands, and kidneys. Modulating these nerves either inwhole (or in part via selective modulation) may enable treatment ofconditions including (but not limited to) diabetes, pancreatitis,obesity, hypertension, obesity related hypertension, hepatitis,hepatorenal syndrome, gastric ulcers, gastric motility disorders,irritable bowel syndrome, and autoimmune disorders such as Crohn'sdisease.

Sympathetic nerves proximate to or encircling the arterial blood vesselknown as the inferior mesenteric artery may pass through the inferiormesenteric ganglion and follow branches of the inferior mesentericartery to innervate the colon, rectum, bladder, sex organs, and externalgenitalia. Modulating these nerves either in whole (or in part viaselective modulation) may enable treatment of conditions including (butnot limited to) GI motility disorders, colitis, urinary retention,hyperactive bladder, incontinence, infertility, polycystic ovariansyndrome, premature ejaculation, erectile dysfunction, dyspareunia, andvaginismus.

While arterial access and treatments have received attention in thisSpecification, the disclosed apparatuses, methods and systems can alsobe used to deliver treatment from within a peripheral vein or lymphaticvessel.

VII. CONCLUSION

The above detailed descriptions of embodiments of the invention are notintended to be exhaustive or to limit the invention to the precise formdisclosed above. Although specific embodiments of, and examples for, theinvention are described above for illustrative purposes, variousequivalent modifications are possible within the scope of the invention,as those skilled in the relevant art will recognize. For example, whilesteps are presented in a given order, alternative embodiments mayperform steps in a different order. The various embodiments describedherein can also be combined to provide further embodiments.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of theembodiments of the invention. Where the context permits, singular orplural terms may also include the plural or singular term, respectively.For example, much of the disclosure herein describes an energy deliveryelement 24 or electrode 46 in the singular. It should be understood thatthis application does not exclude two or more energy delivery elementsor electrodes.

It should also be understood that energy delivery element 24 can be anelectrode, radiofrequency electrode, cooled radiofrequency electrode,thermal element, thermal heating element, electrically resistive heatingelement, cryoablative applicator, microwave antenna, ultrasoundtransducer, high intensity focused ultrasound transducer, or laseremitter.

Additionally, other terms used herein may be expressed in different andinterchangeable ways. For example, a force transmitting section can alsobe an proximal force transmitting section, elongated tubular shaft; afirst flexure zone can also be a flexible tubular structure; adeflectable section can also be an intermediate flexure zone or a secondflexure zone or a deflectable tubular body; a control wire can be aflexure control element; a force dampening section can be a thirdflexure zone or distal flexure zone or passively flexible structure; aforce redirecting element can be a pre-shaped geometry.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the term “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the invention. Accordingly, the invention is notlimited except as by the appended claims.

1-44. (canceled)
 45. A method, comprising: percutaneously introducing aneuromodulation assembly at a distal portion of a treatment deviceproximate to neural fibers innervating a gastrointestinal organ of ahuman subject diagnosed with a gastrointestinal condition; at leastpartially disrupting function of the neural fibers via theneuromodulation assembly; and removing the neuromodulation assembly fromthe subject after treatment, wherein at least partial disruption of thefunction of the neural fibers therapeutically treats the diagnosedgastrointestinal condition.
 46. The method of claim 45 wherein thegastrointestinal condition is an autoimmune disorder or a gastricmotility disorder.
 47. The method of claim 46 wherein thegastrointestinal condition is an autoimmune disorder, and wherein atleast partial disruption of the function of the neural fiberstherapeutically reduces inflammation in the gastrointestinal organ ofthe subject.
 48. The method of claim 46 wherein the gastrointestinalcondition is a gastric motility disorder, and wherein at least partialdisruption of the function of the neural fibers therapeuticallyincreases gastric motility.
 49. The method of claim 46 wherein thegastrointestinal condition is a gastric motility disorder, and whereinat least partial disruption of the function of the neural fiberstherapeutically slows gastric motility.
 50. The method of claim 45wherein the gastrointestinal organ includes at least one of the stomach,the small intestine, the colon, and the rectum of the subject.
 51. Themethod of claim 45 wherein the gastrointestinal condition is at leastone of gastric ulcers, gastric motility disorders, irritable bowelsyndrome, Crohn's disease, and colitis.
 52. The method of claim 45wherein at least partially disrupting function of the neural fibers viathe neuromodulation assembly comprises thermally modulating the neuralfibers via at least one electrode in contact with a vessel wall.
 53. Themethod of claim 45 wherein at least partially disrupting function of theneural fibers via the neuromodulation assembly comprises thermallymodulating the neural fibers via one or more electrodes positionedwithin a gastrointestinal blood vessel of the subject.
 54. A method oftreating a human patient diagnosed with a digestive system condition,the method comprising: intravascularly positioning a neuromodulationassembly within a target blood vessel of the patient and adjacent to atarget sympathetic nerve of the patient; and reducing sympathetic neuralactivity in the patient by delivering energy to the target sympatheticnerve via the neuromodulation assembly, wherein reducing sympatheticneural activity therapeutically treats the patient diagnosed with thedigestive system condition.
 55. The method of claim 54 wherein thedigestive system condition is selected from a group consisting ofCrohn's disease, colitis, pancreatitis, obesity, hepatitis, hepatorenalsyndrome, gastric ulcer, gastric motility disorders, irritable bowelsyndrome, and autoimmune disorders.
 56. The method of claim 54 whereinintravascularly positioning a neuromodulation assembly within a targetblood vessel and adjacent to a target sympathetic nerve comprisespositioning the neuromodulation assembly adjacent the target sympatheticnerve innervating an internal structure of the patient selected from agroup consisting of a stomach, a small intestine, a colon, a rectum, aliver, a gall bladder, a pancreas, a bile duct, an adrenal gland, and akidney.
 57. The method of claim 54 wherein reducing sympathetic neuralactivity in the patient reduces whole body norepinephrine spillover inthe patient.
 58. The method of claim 54 wherein intravascularlypositioning a neuromodulation assembly within a target blood vesselcomprises positioning the neuromodulation assembly in at least one ofthe celiac trunk, the superior mesenteric artery, the inferiormesenteric artery and an abdominal blood vessel.
 59. The method of claim54 wherein reducing sympathetic neural activity in the patient bydelivering energy to the target sympathetic nerve comprises at leastpartially inhibiting afferent neural activity.
 60. The method of claim54 wherein reducing sympathetic neural activity in the patient bydelivering energy to the target sympathetic nerve comprises at leastpartially inhibiting efferent neural activity.
 61. The method of claim54 wherein reducing sympathetic neural activity in the patient bydelivering energy to the target sympathetic nerve comprises partiallyablating the target sympathetic nerve.
 62. The method of claim 54wherein reducing sympathetic neural activity in the patient bydelivering energy to the target sympathetic nerve via theneuromodulation assembly comprises delivering an energy field to thetarget sympathetic nerve via the neuromodulation assembly.
 63. Themethod of claim 62 wherein delivering an energy field to the targetsympathetic nerve comprises delivering at least one of radio frequencyenergy, ultrasound energy, high intensity ultrasound energy, laserenergy, and microwave energy via the neuromodulation assembly.
 64. Themethod of claim 54, further comprising removing the neuromodulationassembly from the patient after delivering energy to the targetsympathetic nerve via the neuromodulation assembly.
 65. A method oftreating a human patient diagnosed with obesity, the method comprising:intravascularly positioning a neuromodulation assembly within a targetblood vessel of the patient and adjacent to a target sympathetic nerveof the patient; and reducing sympathetic neural activity in the patientby delivering energy to the target sympathetic nerve via theneuromodulation assembly to modulate the target sympathetic nerve,wherein modulating the target sympathetic nerve therapeutically treatsthe patient diagnosed with obesity.
 66. The method of claim 65 whereinthe target sympathetic nerve comprises a sympathetic nerve innervating astomach of the patient.
 67. The method of claim 65 whereinintravascularly positioning a neuromodulation assembly within a targetblood vessel comprises positioning the neuromodulation assembly in theceliac trunk or a branch thereof.
 68. The method of claim 65 whereinintravascularly positioning a neuromodulation assembly within a targetblood vessel comprises positioning the neuromodulation assembly in atleast one of the superior mesenteric artery, the inferior mesentericartery, or a branch thereof.
 69. The method of claim 65 wherein thepatient is further diagnosed with obesity-related hypertension, andwherein reducing sympathetic neural activity in the patient furtherresults in a therapeutically beneficial reduction in blood pressure ofthe patient.
 70. The method of claim 65 wherein reducing sympatheticneural activity in the patient by delivering energy to the targetsympathetic nerve comprises thermally modulating the target sympatheticnerve of the patient via an intravascularly positioned catheter carryingone or more electrodes.
 71. The method of claim 65 wherein modulatingthe target sympathetic nerve therapeutically causes a reduction in bodyweight of the patient diagnosed with obesity.